Research2019-05-10T11:22:15-04:00

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For your convenience, Research articles are organized in the following categories. Click on the category for the respective research articles.

More Research on Stem Cells Than Any Other Topic in Science or Medicine

UMBILICAL CORD / WHARTON’S JELLY

Immunosuppressive properties of mesenchymal stromal cells derived from amnion, placenta, Wharton’s jelly and umbilical cord.

https://www.ncbi.nlm.nih.gov/pubmed/23176558

  • CONCLUSION:
  • The results obtained from this study suggest that MSC from amnion, placenta, Wharton’s jelly and umbilical cord can therefore be potentially used for substituting BM-MSC in several therapeutic applications, including the treatment of GvHD.

Immune characterization of mesenchymal stem cells in human umbilical cord Wharton’s jelly and derived cartilage cells

https://www.sciencedirect.com/science/article/abs/pii/S0008874912001220 

  • The hWJMSC has very low immunogenicity and good potential to tolerate rejection. Their intermediate state between adult and embryonic stem cells makes them an ideal candidate for reprogramming to the pluripotent status.

A comparison of human bone marrow-derived mesenchymal stem cells and human umbilical cord-derived mesenchymal stromal cells for cartilage tissue engineering.

https://www.ncbi.nlm.nih.gov/pubmed/19260778

  • Therefore, it was concluded that hUCMSCs may be a desirable option for use as a mesenchymal cell source for fibrocartilage tissue engineering, based on abundant type I collagen and aggrecan production of hUCMSCs in a 3D matrix, although further investigation of signals that best promote type II collagen production of hUCMSCs is warranted for hyaline cartilage engineering.

Comparison of human mesenchymal stem cells derived from dental pulp, bone marrow, adipose tissue, and umbilical cord tissue by gene expression.

https://www.ncbi.nlm.nih.gov/pubmed/24145770

  • Comparison of human mesenchymal stem cells derived from dental pulp, bone marrow, adipose tissue, and umbilical cord tissue by gene expression.
  • All MSCs tested were phenotypically similar and of fibroblastoid morphology. DP-MSCs and UBC-MSCs were more proliferative than bone marrow BM-MSCs and AT-MSCs.

Ultrastructural and immunocytochemical analysis of multilineage differentiated human dental pulp- and umbilical cord-derived mesenchymal stem cells.

https://www.ncbi.nlm.nih.gov/pubmed/21124001 

  • Our results demonstrate, at the biochemical and ultrastructural level, that DPSC display at least bilineage potential, whereas UCSC, which are developmentally more primitive cells, show trilineage potential. We emphasize that transmission electron microscopical analysis is useful to elucidate detailed structural information and provides indisputable evidence of differentiation. These findings highlight their potential therapeutic value for cell-based tissue engineering.

Endothelial differentiation of Wharton’s jelly-derived mesenchymal stem cells in comparison with bone marrow-derived mesenchymal stem cells.

https://www.ncbi.nlm.nih.gov/pubmed/19375653 

  • CONCLUSION: These results showed that UC-MSCs had higher endothelial differentiation potential than BM-MSCs. Therefore, UC-MSCs are more favorable choice than BM-MSCs for neovascularization of engineered tissues.

Feasibility, Safety, and Tolerance of Mesenchymal Stem Cell Therapy for Obstructive Chronic Lung Allograft Dysfunction

https://stemcellsjournals.onlinelibrary.wiley.com/doi/10.1002/sctm.17-0198 

  • Conclusion: The results of our study suggest it is safe and feasible to provide cell therapy with intravenous infusion of bone marrow‐derived MSCs to lung transplant recipients with moderate obstructive CLAD, warranting future studies to assess the effectiveness of this therapy for management of acute or chronic graft dysfunction.

Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy.

https://www.ncbi.nlm.nih.gov/pubmed/25622293 

  • The human umbilical cord is a promising source of mesenchymal stem cells (HUCMSCs). Unlike bone marrow stem cells, HUCMSCs have a painless collection procedure and faster self-renewal properties. Different derivation protocols may provide different amounts and populations of stem cells. Stem cell populations have also been reported in other compartments of the umbilical cord, such as the cord lining, perivascular tissue, and Wharton’s jelly. HUCMSCs are noncontroversial sources compared to embryonic stem cells. They can differentiate into the three germ layers that promote tissue repair and modulate immune responses and anticancer properties. Thus, they are attractive autologous or allogenic agents for the treatment of malignant and nonmalignant solid and soft cancers. HUCMCs also can be the feeder layer for embryonic stem cells or other pluripotent stem cells.

Comparative Characterization of Cells from the Various Compartments of the Human Umbilical Cord Shows that the Wharton’s Jelly Compartment Provides the Best Source of Clinically Utilizable Mesenchymal Stem Cells

https://neomatrixmedical.com/wp-content/uploads/2018/05/2015-Singapore-Mesenchymal-Stem-Cells-From-Umbilical-Cord-Tissue-Are-Best-in-Clinical-Applicatoins-2.pdf

  • Taken together, it appears that MSCs from the WJ are more superior than those from the PV, SA, AM and MC in terms of clinical utility and research value because (i) their isolation is simple, quick and easy to standardize, (i) they have lesser non-stem cell contaminants (iii) they are rich in stemness characteristics, (iv) they can be generated in large numbers with minimal manipulation, (v) they are proliferative and (vi) have broad and efficient differentiation potential.
    They will thus be stable and attractive candidates for research and future cell-based therapies when derived, propagated and characterized correctly. Our results show that when isolating MSCs from the UC, the WJ should be the preferred compartment, and a standardized method of derivation must be used so as to make meaningful comparisons of data between research groups.

Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC

https://neomatrixmedical.com/wp-content/uploads/2018/05/Comparison-of-Adult-and-Neonatal-Tissue-MSCs_Hass_2011-copy.pdf

  • In contrast, the umbilical cord tissue or Wharton’s jelly is an excellent source for isolating MSC [103-105]. Source-related features of MSC might directly contribute to the diversity of opinions regarding the mechanisms (soluble factors versus cell-to-cell contact) of MSC-mediated immunomodulation

The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood

https://neomatrixmedical.com/wp-content/uploads/2018/05/Umbilical-Cord-vs-Blood-MSC-source.Zeddou2010-copy.pdf

  • Conclusion According to the critical parameters of sample selection described in the literature, and using different culture media proposed to enhance the growth of MSC, in parallel with the use of different methods of cell isolation, we were not able to establish MSC cultures from more than one out of 15 UCB samples. Given the high frequency of MSC in UCM, we hypothesize that there may be MSC contamination while collecting cord blood. This may explain the rare described cases where MSC isolation from UCB has been possible. However, it could not be ascertained whether the collection method may have caused the disappearance of circulating MSC from the cord blood MNC compartment in favor of the endothelial/subendothelial layer of the UCM. Anyway, UCB can be excluded as a reliable source of MSC in favor of the richer and more reproducible source that is the UCM.

Umbilical Cord Tissue Offers the Greatest Number of Harvestable Mesenchymal Stem Cells for Research and Clinical Application: A Literature Review of Different Harvest Sites

https://neomatrixmedical.com/wp-content/uploads/2018/05/Umbilical-Cord-WJ-greatest-_-MSC.VANGSNESS2015-copy.pdf

  • Large variations in cell harvest yields remain for each major tissue site for MSCs as reported in the literature to date. Reviewed research supports the understanding that placental tissue provides the highest concentration of cells whereas adipose tissue offers the highest levels of autologous cells. Consequently, considerations must be made regarding the non-autologous nature of umbilical cord derived stem cells, as well as the increased post-harvest processing required for adipose-derived stem cells, for the purposes of research and clinical application.

Discarded Wharton’s Jelly of the Human Umbilical Cord: A Viable Source for Mesenchymal Stem Cells

https://neomatrixmedical.com/wp-content/uploads/2018/05/Umbilical-Cord-WJ-viable-MSC.Watson2015-copy.pdf

  • In particular, WJ is a predominantly good source of cells because MSCs in WJ (WJ-MSC) are maintained in a very early embryological phase and therefore have retained some of the primitive stemness properties. WJ-MSCs can easily differentiate into a plethora of cell types leading to a variety of applications. WJ-MCSs are still the ideal future for cell therapy; their properties of high proliferation capability and versatility to differentiate between three lineages allow them to lower immunogenicity and have the potential to treat an array of diseases and disorders

Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy

https://neomatrixmedical.com/wp-content/uploads/2018/05/Umbilical-Cord-as-Prospective-Source-for-Mesenchymal-Stem-Cell-Based-Therapy-1.pdf

  • Conclusion The human umbilical cord is a source of MSCs that have Currently isolated and cultured umbilical cord MSCs are a promising storage object of the leading biobanks of the world, and the number of registered clinical trials on their use is currently growing.

Human Umbilical Cord-Derived Mesenchymal Stem Cells Do Not Undergo Malignant Transformation during Long-Term Culturing in Serum-Free Medium

https://neomatrixmedical.com/wp-content/uploads/2018/05/Human-Umbilical-Cord-Derived-Mesenchymal-Stem-Cells-Do-Not-Undergo-Malignant-Tr.pdf

  • Results Flow cytometry analysis showed that very high expression was detected for CD105, CD73, and CD90 and very low expression for CD45, CD34, CD14, CD79a, and HLA-DR. MSCs could differentiate into osteocytes, chondrocytes, and adipocytes in vitro. There was no obvious chromosome elimination, displacement, or chromosomal imbalance as determined from the guidelines of the International System for Human Cytogenetic Nomenclature. Telomerase activity was down-regulated significantly when the culture time was prolonged. Further, no tumors formed in rats injected with hUC-MSCs (P ) cultured in serum-free and in serum containing conditions. Conclusion Our data showed that hUC-MSCs met the International Society for Cellular Therapy sandards for conditions of long-term in vitro culturing at P . Since hUC-MSCs can be safely expanded in vitro and are not susceptible to malignant transformation in serum-free medium, these cells are suitable for cell therapy.

Comparative Analysis Of Bone Marrow and Wharton’s Jelly Mesenchymal Stem/Stromal Cells

http://www.bloodjournal.org/content/122/21/1212?sso-checked=true

  • Taken together WJ-MSCs display decreased cellular senescence after extended in vitro culture, increased proliferative capacity and reduced potential to differentiate in vitro to adipocytes and osteocytes, as compared to BM-MSCs. The last two observations can be explained, at least partly, by the aberrant expression of Wnt-signaling molecules in WJ-MSCs. The emerging role of Wnt-signaling pathway in WJ-MSC biology is currently under investigation.

Mesenchymal stem cells derived from Wharton’s Jelly of the umbilical cord: biological properties and emerging clinical applications.

https://www.ncbi.nlm.nih.gov/pubmed/23279098

  • Thus, there is accumulating interest in identifying alternative sources for MSCs. To this end MSCs obtained from the Wharton’s Jelly (WJ) of umbilical cords (UC) have gained much attention over the last years since they can be easily isolated, without any ethical concerns, from a tissue which is discarded after birth. Furthermore WJ-derived MSCs represent a more primitive population than their adult counterparts, opening new perspectives for cell-based therapies. In this review we will at first give an overview of the biology of WJ-derived UC-MSCs. Then their potential application for the treatment of cancer and immune mediated disorders, such graft versus host disease (GVHD) and systemic lupus erythematosus (SLE) will be discussed, and finally their putative role as feeder layer for ex vivo hematopoietic stem cell (HSC) expansion will be pointed out.

Wharton’s Jelly Derived Mesenchymal Stem Cells: Future of Regenerative Medicine? Recent Findings and Clinical Significance

https://www.hindawi.com/journals/bmri/2015/430847/

  • Taken together, the clinical implication of oxidative stress, telomere length, DNA damage and disease is impaired therapeutic potential of MSC isolated from aged patients. These changes in MSC biology indicate that aged patients may require an alternative source of stem cells for treatment. The high efficiency of WJ-MSC recovery, the minimal ethical concerns associated with its acquirement and use, low immunogenicity, and the fact that they are from healthy, young donors make them an ideal source of MSC for autologous and allogeneic applications.

Wharton’s jelly as a reservoir of peptide growth factors.

https://www.ncbi.nlm.nih.gov/pubmed/16226124

  • The amounts of peptide growth factors calculated per microgram of DNA are distinctly higher in Wharton’s jelly in comparison to the umbilical cord artery. Western blot analysis demonstrated that almost the entire amount of these factors is bound to high molecular weight components. Since the number of cells in Wharton’s jelly is very low and the amounts of extracellular matrix components are very high, it is concluded that the cells are strongly stimulated by peptide growth factors to produce large amounts of collagen and glycosaminoglycans.

NEUROPATHY

Enhanced neuro-therapeutic potential of Wharton’s Jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture.

https://www.ncbi.nlm.nih.gov/pubmed/26971678  

  • In order to determine the variable responses to MSCs therapy, the present study examines and compares the adhesive stromal cells from immature perinatal tissues—umbilical cord Wharton’s Jelly (WJ-MSC) and from adult, healthy donors of bone marrow origin (BM-MSC).
    • WJ-MSC represent an example of immature type of “pre-MSC” population with exceptionally high commitment to neural differentiation.
    • WJ-MSC exhibit a higher proliferation rate, a greater expansion capability and enhanced neurotrophic factors expression in comparison to BM-MSC.
    • Hypoxia conditions accelerated WJ cells growth together with a regression of cell differentiation/maturation.
    • The cultures of hypo-oxygenated BM-MSC do not express any of the phenomena mentioned above, except for the moderate stimulation of cell growth.

Human umbilical cord Wharton’s Jelly-derived mesenchymal stem cells differentiation into nerve-like cells.

https://www.ncbi.nlm.nih.gov/pubmed/16336835 

  • CONCLUSIONS:MSCs could be isolated from human umbilical cord Wharton’s Jelly. They were capable of differentiating into nerve-like cells using Salvia miltiorrhiza or beta-mercaptoethanol. The induced MSCs not only underwent morphologic changes, but also expressed the neuron-related genes and neuronal cell markers. They may represent an alternative source of stem cells for central nervous system cell transplantation

Perspectives of employing mesenchymal stem cells from the Wharton’s jelly of the umbilical cord for peripheral nerve repair.

https://www.ncbi.nlm.nih.gov/pubmed/24083432  

  • Mesenchymal stem cells (MSCs) from Wharton’s jelly present high plasticity and low immunogenicity, turning them into a desirable form of cell therapy for the injured nervous system. Their isolation, expansion, and characterization have been performed from cryopreserved umbilical cord tissue. The MSCs from Wharton’s jelly delivered through tested biomaterials should be regarded a potentially valuable tool to improve clinical outcome especially after trauma to sensory nerves. In addition, these cells represent a noncontroversial source of primitive mesenchymal progenitor cells, which can be harvested after birth, cryogenically stored, thawed, and expanded for therapeutic uses.

Stem Cell Technology for Neurodegenerative Diseases

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177143/

  • Cellular therapies offer great promise for the treatment of these diseases, and research progress to date supports the utilization of stem cells to offer cellular replacement and/or provide environmental enrichment to attenuate neurodegeneration. In diseases where specific subpopulations of cells or widespread neuronal loss are present, cellular replacement may reproduce or stabilize neuronal networks. In addition, environmental enrichment may provide neurotrophic support to remaining cells or prevent the production or accumulation of toxic factors that harm neurons. In many cases, cellular therapies provide beneficial effects through both mechanisms.

Human mesenchymal stem cells improve the neurodegeneration of femoral nerve in a diabetic foot ulceration rats

https://www.sciencedirect.com/science/article/abs/pii/S0304394015003377?via%3Dihub

  • These data suggested that hMSCs-UC-treatment partially reverse the neuronal degeneration and nerve function of FN, which might be contributed by the upregulation of NGF with dramatic angiogenesis in FN-innervated gastrocnemius, consequently reversing neuronal structure and function, preventing or curing foot ulceration.

Stem Cells for the Treatment of Neuropathic Pain

http://www.japmnet.com/uploadfile/2017/0121/20170121044012254.full.pdf

  • Stem cell transplantation can effectively relieve neuropathic pain under different pathological conditions. However, it is interesting to point out that peripheral neuropathic pain seems to be more responsive to stem cell therapy than SCI (Spinal Cord Injury) induced chronic pain. Moreover, stem cell treatment does not always exert positive results in SCI- induced chronic pain (e.g. aggravating pain above the lesion spinal cord segment).

Mesenchymal stem cells to treat diabetic neuropathy: a long and strenuous way from bench to the clinic

https://www.researchgate.net/publication/306435063_Mesenchymal_stem_cells_to_treat_diabetic_neuropathy_a_long_and_strenuous_way_from_bench_to_the_clinic

  • CONCLUSION DN (Diabetic Neuropathy) frequently leads to foot ulcers and ultimately limb amputations without effective clinical therapy. DN is characterized by reduced  vascularity in the peripheral nerves and deficiency in angiogenic and neurotrophic factors. Only delivering neurotrophic or angio-genic factors for treatment in the form of protein or gene therapy is very modest if not ineffective. MSCs have been highlighted as a new emerging regenerative therapy owing to their multipotency for DN.MSCs reverse manifestations of DN, repair tissue, and anti-hyperglycemia. MSCs also paracrinely secrete neurotrophic factors, angio-genic factors, cytokines, and immunomodulatory substances to ameliorate DN.

Mesenchymal Stem Cells as a Prospective Therapy for the Diabetic Foot

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102750/

  • In summary, MSC transplantation is a new technology that can be used to treat the diabetic foot and is a well-studied topic in the field of angiogenesis. MSCs have high proliferative and self-renewal capabilities in addition to the ability to differentiate into multiple types of cells, including VECs, SMCs, and astrocytes and, to a lesser extent, oligodendrocytes and Schwann cells, after transplantation. The transplanted stem cells regulate the immune system by influencing the immune responses of T cells, natural killer cells, macrophages, and dendritic cells, and they participate in diabetic wound healing. Via both endocrine and paracrine effects and the secretion of angiogenic factors, cytokines and neurotrophic factors that promote angiogenesis, the blood flow in the local tissue recovers, and neurological lesions are healed. MEX also participate in the wound healing process via the effects of the mRNA, miRNA, and protein molecules which they contain (Figures  (Figures1,1 ,2,2, and  and3).3). Although certain researchers argue that transplanted MSCs can also recover islet β cell dysfunction and maintain balanced blood glucose levels, these phenomena seem to lack supporting evidence [172]. In animals with diabetic feet and in clinical trials, the transplantation of MSCs has led to positive results, and, in short-term follow-ups, there have been no significant adverse reactions or serious complications. The MSC transplantation technique has therefore been successfully developed, and it provides a basis for clinical applications involving stem cell transplantation to treat the diabetic foot.

Effect of subcutaneous treatment with human umbilical cord blood-derived multipotent stem cells on peripheral neuropathic pain in rats

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343048/

  • We demonstrated that hUCB-MSCs showed a significant improvement in animal models for neuropathic pain after intraplantar, subcutaneous transplantation. It seems that hUCB-MSCs transplantation cause secretion of TIMP-2, which inhibits MMP 2 activation that otherwise produces neuropathic pain symptoms, via IL-βcleavage and activation of p-ERK in astrocytes [21]. This finding was indirectly confirmed by expression of c-fos and CGRP, which are generally used as stress markers p-ERK, which is upstream of c-fos and CGRP. Among three animal models for neuropathic pain, spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats. The CCI model has been extensively used for many neuropathic studies because it closely mimics the clinical nerve injury conditions and pain nature such as complex regional pain syndrome type 2

Perspectives of employing mesenchymal stem cells from the Wharton’s jelly of the umbilical cord for peripheral nerve repair.

https://www.ncbi.nlm.nih.gov/pubmed/24083432

  • Mesenchymal stem cells (MSCs) from Wharton’s jelly present high plasticity and low immunogenicity, turning them into a desirable form of cell therapy for the injured nervous system. Their isolation, expansion, and characterization have been performed from cryopreserved umbilical cord tissue.

ORTHOPEDIC CONDITIONS / SPORTS INJURIES

Characteristics of mesenchymal stem cells derived from Wharton’s jelly of human umbilical cord and for fabrication of non-scaffold tissue-engineered cartilage.

https://www.ncbi.nlm.nih.gov/pubmed/23899897 

  • The human WMSCs express characteristics of pre-chondrocytes, low immunogenicity and are easy to be obtained with higher purity because there have no hematopoietic cells in Wharton’s jelly, so it may be a new seed cells more suitable for constructing tissue-engineered cartilage.

Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration

https://www.sciencedirect.com/science/article/pii/S1046202315300918?via%3Dihub 

  • In addition, WJSCs has several advantages that make them an attractive choice for use in tissue engineering and regenerative medicine. WJSCs (i) are a relatively young cell type compared to most other MSCs, (ii) have no ethical concerns unlike ESCs, (iii) can be harvested painlessly unlike bone-marrow MSCs, (iv) share few embryonic features, (v) have high cell proliferation, (vi) have wide differentiation potential, (vii) are hypo-immunogenic and (viii) are non-tumorigenic [61], [62], [63], [64], [65], [66], [67]. Developmentally, the umbilical cord and its contents are embryonic in nature as it arises from the epiblast, which also give rise to the three primordial germ layers, the amnion and the allantois. Therefore, WJSCs come to occupy an intermediate position between the most versatile pluripotent ESCs/iPSCs and adult tissue specific MSCs, which might explain the presence of some embryonic stem features and increased stemness.
  • WJSCs, by their inherent nature have high hyaluronic acid, sulfated glycosaminoglycans (GAGs) and collagen expression [73], which to some extent reflect native cartilage tissue. Moreover, uses of WJSCs following their differentiation into multiple cell types as reported by many different research groups, with some progressing on to clinical trials is encouraging [74], [75], [76] and justify the use of WJSCs in cartilage regeneration procedures.

Regeneration of Full‐Thickness Rotator Cuff Tendon Tear After Ultrasound‐Guided Injection With Umbilical Cord Blood‐Derived Mesenchymal Stem Cells in a Rabbit Model

https://stemcellsjournals.onlinelibrary.wiley.com/doi/10.5966/sctm.2015-0040

  • Conclusion UCB‐derived MSC injection under ultrasound guidance without surgical repair or bioscaffold resulted in the partial healing of full‐thickness rotator cuff tendon tears in a rabbit model. Histology revealed that UCB‐derived MSCs induced regeneration of rotator cuff tendon tears and that the regenerated tissue was predominantly composed of type I collagens. In addition, motion analysis showed better walking capacity after MSC injection than HA or normal saline injection. These results suggest that ultrasound‐guided UCB‐derived MSC injection may be a useful conservative treatment for full‐thickness rotator cuff tendon tear repair.

Human umbilical cord-derived mesenchymal stem cells reduce monosodium iodoacetate-induced apoptosis in cartilage

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968746/ 

  • Based on the present findings, we conclude that HUCMSCs can fulfill MSC characteristics with mesoderm differentiation capability. HUCMSCs can assist MIA-treated mice in regeneration of hyaline cartilage and/or repair of cartilage damage and in ameliorating cartilage apoptosis. These effects can be associated with motor behavioral improvement. Thus, HUCMSCs may be a feasible source for stem cell treatment for OA cartilage repair.

Effects of insulin-like growth factor-induced Wharton jelly mesenchymal stem cells toward chondrogenesis in an osteoarthritis model.

https://www.ncbi.nlm.nih.gov/pubmed/30140415

  • Effects of insulin-like growth factor-induced Wharton jelly mesenchymal stem cells toward chondrogenesis in an osteoarthritis model.
    CONCLUSION: The IGF1-induced WJMSCs were capable to enhance chondrogenesis, indicated by increased expression of SOX9 and COL2 and decreased expression of ADAMTS1, ADAMTS5, MMP3, MMP1, and RANKL. These findings can be further used in the osteoarthritis treatment.

Effect of nicotine on the proliferation and chondrogenic differentiation of the human Wharton’s jelly mesenchymal stem cells.

https://www.ncbi.nlm.nih.gov/pubmed/28372298 

  • Effect of nicotine on the proliferation and chondrogenic differentiation of the human Wharton’s jelly mesenchymal stem cells. CONCLUSIONS: At the concentration used, nicotine had an adverse effect on the proliferation and chondrogenic differentiation of hWJ-MSCs which was probably impaired through a α7 nAChR mediation

Human Wharton’s Jelly Mesenchymal Stem Cells Maintain the Expression of Key Immunomodulatory Molecules When Subjected to Osteogenic, Adipogenic and Chondrogenic Differentiation In Vitro: New Perspectives for Cellular Therapy

https://neomatrixmedical.com/wp-content/uploads/2018/12/Human-whartons-jelly-MSCs-maintain-the-expression-of-key-immunomodulatory.pdf

  • Human Wharton’s Jelly Mesenchymal Stem Cells Maintain the Expression of Key Immunomodulatory Molecules When Subjected to Osteogenic, Adipogenic and Chondrogenic Differentiation In Vitro: New Perspectives for Cellular Therapy “This strongly suggests that also after the acquisition of a mature phenotype, WJ-MSCs-derived cells may maintain their immune privilege. This evidence, which deserves much work to be confirmed in vivo and in other MSCs populations, may provide a formal proof of the good results globally achieved with WJMSCs as cellular therapy vehicle.”

Cartilage Repair in the Knee Using Umbilical Cord Wharton’s Jelly–Derived Mesenchymal Stem Cells Embedded Onto Collagen Scaffolding and Implanted Under Dry Arthroscopy

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852271/

  • Cartilage Repair in the Knee Using Umbilical Cord Wharton’s Jelly–Derived Mesenchymal Stem Cells Embedded Onto Collagen Scaffolding and Implanted Under Dry Arthroscop
  • Although WJ-MSCs are allogeneically sourced, they are considered weakly immunogenic or non-immunogenic because of the low expression of HLA class I. The ability of these cells to promote chondrogenesis, without eliciting an immunogenic response, makes them an excellent candidate for providing cell-based cartilage repair in an off-the-shelf fashion. Moreover, use of WJ-MSCs for cartilage repair in older patients will address concerns related to MSC number and immunomodulatory capacity with autologous harvest in aging patients, making this technique a promising advancement in the treatment of cartilage injury for this demographic

Role of mesenchymal stem cells in osteoarthritis treatment

https://www.sciencedirect.com/science/article/pii/S2214031X17300074

  • Role of mesenchymal stem cells in osteoarthritis treatment
  • Without an effective cure, OA remains a significant clinical burden on our elderly population. The advancement of regenerative medicine and innovative stem cell technology offers a unique opportunity to treat this disease. In this review, we examine OA and the likely resolution with MSCs. MSCs have been one of the highlights in stem cell research in recent years. Although the application of MSCs in joint repair is well established, it is particularly exciting about MSCs being used for OA treatment.

Mesenchymal stem cells for cartilage regeneration in osteoarthritis

https://www.wjgnet.com/2218-5836/full/v8/i9/674.htm

  • In summary, these studies show that MSCs can be employed successfully to treat mild to moderate OA through various ways. They provide alternative treatment options and treatment can start early during progression of OA. The traditional major surgeries used to treat late stages are expensive and come with risks. The less invasive techniques outlined in this minireview have revealed good outcomes, but the field merits further investigation. Superior outcome was evident with greater quantity of MSCs injected. Allogenic cells from healthy young donors can also be utilized. These findings have further empowered researchers to investigate the potentials of MSCs for tissue engineering and a number of clinical trials are now underway. Most of the emphasis on minimally invasive therapeutic alternatives including intraarticular injections of MSCs, aim to cut out cost and risks of major surgeries. Additional investigations are warranted to validate the safety and efficiency of different application before a standardized treatment regimen can be established.

EYE CONDITIONS

A Promising Tool in Retina Regeneration: Current Perspectives and Challenges When Using Mesenchymal Progenitor Stem Cells in Veterinary and Human Ophthalmological Applications

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602072/ 

  • Stem cells have been investigated in opthalmological research as a forthcoming tool for retinal degeneration. Mesenchymal stem cells have exhibited many advantages because of their multilineage differentiation potential, the ease in their culturing and their immunomodulatory properties which are crucial in retinal regeneration research. Current exploration has determined new mechanisms of regeneration and MSC protective capabilities, on degeneration of different types of retinal cell ad retinal vessels. Mesenchymal stem cell-derived microvesicles (MVs) allow for developments in future research and clinical applications as a result of their availability as well as the growth factors, miRNA and mRNA they possess. Studies have shown that the application of MVs in regenerative medicine proves to be very dynamic, which is directing clinical research in opthamology towards this domain of study. In the grand scheme of scientific interest, it is expected that MVs may have higher output and potential in retinal regeneration than stem cell therapies have so far, therefore it is anticipated that this research field will be moving further into this direction.

Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases.

https://www.ncbi.nlm.nih.gov/pubmed/29774506 

  • Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases. .In conclusion, MSC-derived exosomes represent potentially new therapeutic agents in the therapy of degenerative and inflammatory ocular diseases.

E.D. (Erectyle Dysfunction)

BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells promote erectile function in a rat model of cavernous nerve electrocautery injury.

https://www.ncbi.nlm.nih.gov/pubmed/26577999   

  • CONCLUSIONS: Intracavernous injection of BDNF-hypersecreting hUCB-MSCs can enhance the recovery of erectile function, promote the CNs regeneration and inhibit corpus cavernosum fibrosis after CNEI in a rat model.

Erectile dysfunction treated with intracavernous stem cells: A promising new therapy?

https://www.ncbi.nlm.nih.gov/pubmed/30300133

  • The main cause involved in the pathophysiology of erectile dysfunction is vascular damage related to endothelial and neuronal injury. The interest in stem cell therapy is justified by their capability to differentiate into specific damaged tissues, including endothelium and nervous tissue, and induction of the host own cell proliferation.

Stem-cell therapy for erectile dysfunction.

https://www.ncbi.nlm.nih.gov/pubmed/26558088   

  • RESULTS: Fifty-four papers were identified and contributed, either as an original research report or review thereof, to this review. Several preclinical studies addressed SC-based therapies for the recovery of erectile function caused by a variety of both chronic and acute conditions. Overall, these studies showed beneficial effects of SC therapy, while evidence on the mechanisms of action of SC therapy varied between studies. One clinical trial investigated the short-term effects of SC therapy in diabetic patients with ED. Two more clinical trials are currently recruiting patients.
  • CONCLUSIONS: The rapidly expanding and highly promising body of preclinical work on SC-based medicine providing a potential cure for ED, rather than merely symptom relief, is indicative of the increasing interest in regenerative options for sexual medicine over the past decade. Clinical trials are currently recruiting patients to test the preclinical results in men with ED.

Stem Cell Therapy for Erectile Dysfunction: Progress and Future Directions.

https://www.ncbi.nlm.nih.gov/pubmed/27784560 

  • RESULTS: Several preclinical studies have addressed stem cell-based therapies for the recovery of erectile function following cavernous nerve injury and in Peyronie’s disease, diabetes, aging, and hyperlipidemia. Overall, these studies have shown beneficial effects of stem cell therapy, while evidence on the mechanisms of action of stem cell therapy still varies between studies.
  • While many authors propose engraftment and differentiation of stem cells, a recent paradigm shift toward paracrine mechanisms of action is observed

Multipotent stromal cell therapy for cavernous nerve injury-induced erectile dysfunction.

https://www.ncbi.nlm.nih.gov/pubmed/22145667 

  • RESULTS: MSCs from both bone marrow and adipose tissue have shown beneficial effects in a variety of animal models for ED. While MSC application in chronic disease models such as diabetes, aging, and hyperlipidemia may result in cell engraftment and possibly MSC differentiation, this observation has not been made in the acute CNI rat model. In the latter setting, MSC effects seem to be established by cell recruitment toward the major pelvic ganglion and local paracrine interaction with the host neural tissue.
  • CONCLUSIONS: While the type of model may influence the mechanisms of action of this MSC-based therapy, MSCs generally display efficacy in various animal models for ED.

Stem cell therapies in post-prostatectomy erectile dysfunction: a critical review.

https://www.ncbi.nlm.nih.gov/pubmed/28263125 

  • CONCLUSION: MSC therapy consistently improved erectile functions after CNI. There seems to be a consensus on the disease model used and outcome evaluation however further studies focusing on immunologic response to MSCs, their mechanism of action and in vivo fate are needed before their widespread use in clinic.

Advances in stem cell research for the treatment of male sexual dysfunctions.

https://www.ncbi.nlm.nih.gov/pubmed/26759972 

  • SUMMARY: Evidence from preclinical studies has established stem cells as a potential curative treatment for erectile dysfunction and early phase clinical trials are currently performed.

Stem Cells in Male Sexual Dysfunction: Are We Getting Somewhere?

https://www.ncbi.nlm.nih.gov/pubmed/28041853

  • CONCLUSION: Stem cells have an established efficacy in preclinical studies and early clinical trials. Studies are currently being published demonstrating the safety of intrapenile injection of autologous bone marrow- and adipose tissue-derived stem cells.

MSC-derived exosomes ameliorate erectile dysfunction by alleviation of corpus cavernosum smooth muscle apoptosis in a rat model of cavernous nerve injury.

https://www.ncbi.nlm.nih.gov/pubmed/30257719 

  • CONCLUSIONS: Exosomes isolated from MSCs culture supernatants by ultracentrifugation could ameliorate CNI-induced ED in rats by inhibiting apoptosis in CCSMCs, with similar potency to that observed in the MSCs-treated group. Therefore, this cell-free therapy has great potential for application in the treatment of CNI-induced ED for replacing cell therapy. MSC-derived exosomes ameliorate erectile dysfunction in a rat model of cavernous nerve injury.

Additional Research:

The following are research articles with promising results for auto-immune conditions, cancer, COPD, and other. Please note that we are excited about the future of stem cell therapy but we DO NOT offer treatment at Neo Matrix Medical for these conditions.

Treatment of Psoriasis with Mesenchymal Stem Cells

https://www.amjmed.com/article/S0002-9343(15)01043-8/fulltext 

  • Unexpectedly, his skin lesions, as well as engraftment, recovered day by day. Six months later, the patient’s lymphoma underwent complete remission and his psoriasis was significantly relieved (Figure A.2). The skin returned to normal within 12 months (Figure A.3). Now the patient has been monitored for nearly 5 years. His condition remains stable, with no recurrence of lymphoma or psoriasis.

Neural differentiation and potential use of stem cells from the human umbilical cord for central nervous system transplantation therapy.

https://www.ncbi.nlm.nih.gov/pubmed/18241062 

  •  Recent findings also suggest that neurons derived from cord stroma mesenchymal cells could alleviate movement disorders in hemiparkinsonian animal models. We review here the neurogenic potential of umbilical cord stem cells and discuss possibilities of their exploitation as an alternative to human embryonic stem cells or neural stem cells for transplantation therapy of traumatic CNS injury and neurodegenerative diseases.

Discarded Wharton’s Jelly of the Human Umbilical Cord: A Viable Source for Mesenchymal Stem Cells

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274214/

  • WJ-MCSs are still the ideal future for cell therapy; their properties of high proliferation capability and versatility to differentiate between three lineages allow them to lower immunogenicity and have the potential to treat an array of diseases and disorders
    • Diabetes… Also additional research suggests that WJ-MSC may have the potential to benefit in the direct treatment of diabetes mellitus [38]. By using markers that indicate when certain genes are expressed, models have shown that WJ-MSCs have the capability to differentiate into all sorts of pancreatic cells including the insulin-producing β cells [39]. Using immunohistochemistry and ELISA assays, a significantly greater amount of insulin and C-peptide protein was released from the differentiated cells than from the undifferentiated cells.
    • Liver disease…Transplantation of WJ-MSCs has also been tested in liver fibrosis. Using carbon tetrachloride (CCl4), rats were experimentally induced display liver fibrosis and 4 weeks later received WJ-MSCs injections [22]. After an additional 4 weeks, there was a remarkable decrease in the liver fibrosis in the rats treated with WJ-MSCs as compared to the rats that were not treated with the WJ-MSCs. Some WJ-MSCs exhibited phenotypes of the liver, and those WJ-MSCs that did not differentiate had the capability to secrete cytokines that have the potential to restore liver function [23]. These observations indicate a multi-pronged reparative mechanism of WJ-MSCs involving specific lineage differentiation and therapeutic molecules that are key pathways towards tissue repair.

Human Wharton’s Jelly-Derived Stem Cells Display Immunomodulatory Properties and Transiently Improve Rat Experimental Autoimmune Encephalomyelitis.

https://www.ncbi.nlm.nih.gov/pubmed/25310756 

  • Collectively, we show that WJ-MSCs have trophic support properties and effectively modulate immune cell functioning both in vitro and in the EAE model, suggesting WJ-MSC may hold promise for MS therapy.

Role of Nonmuscle Myosin II in Migration of Wharton’s Jelly-Derived Mesenchymal Stem Cells.

https://www.ncbi.nlm.nih.gov/pubmed/25923805 

  • Role of Nonmuscle Myosin II in Migration of Wharton’s Jelly-Derived Mesenchymal Stem Cells.
  • It is the promise of regeneration and therapeutic applications that has sparked an interest in mesenchymal stem cells (MSCs). Following infusion, MSCs migrate to sites of injury or inflammation by virtue of their homing property.

Lung mesenchymal stem cells-derived extracellular vesicles attenuate the inflammatory profile of Cystic Fibrosis epithelial cells.

https://www.ncbi.nlm.nih.gov/pubmed/30076968

  • We conclude that the anti-inflammatory and anti-oxidant efficacy of EVs (extra cellular vesicles) derived from lung MSCs could be mediated by up-regulation of the PPARγ axis, whose down-stream effectors (NF-kB and HO-1) are well-known modulators of these pathways.
  • EVs could be a novel strategy to control the hyper-inflamed condition in Cystic Fibrosis.

Interaction of Wharton’s jelly derived fetal mesenchymal cells with tumor cells.

https://www.ncbi.nlm.nih.gov/pubmed/24804889 

  • Currently, pre-clinical and clinical studies have demonstrated the importance of stem cell based therapies for the treatment of human diseases. Fetal Mesenchymal Stem Cells (Fetal MSCs) are potential candidates that can be utilized for the treatment of different types of cancer. Recently, Wharton’s jelly (umbilical cord matrix) was proved to be a rich source of MSCs and they can be isolated by non-invasive methods such as Ficoll density gradient and antibodies coupled magnetic beads without any ethical issues. Documentation based on various literatures emphasized that fetal MSCs isolated from fetal umbilical cord possess beneficial activity in cancer therapy than adult MSCs. Specific markers of fetal MSCs such as tumor tropism (exhibit tumor microenvironments which act similar to anti inflammation immune cells) and low immunogenicity conferred them as a promising tool in gene therapy based oncology research. Based on these facts, this review summarizes the potential interaction of fetal mesenchymal stem cells with tumor cells and their use in clinical protocols.

Autologous Cellular Therapy and its Effects on COPD: A Pilot Study

https://lunginstitute.com/white-papers/autologous-stem-cell-therapy-and-its-effects-on-copd/

COPD Improves with Stem Cell Therapy

https://copdnewstoday.com/2016/06/28/lung-institute-review-stem-cells-not-a-miracle-cure-for-copd-but-still-improving-lives/

Stem cell therapies for chronic obstructive pulmonary disease: current status of pre-clinical studies and clinical trials

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864644/ 

  • In summary, the approaches discussed for regenerative therapies have demonstrated positive effects in COPD animal models and have been safe in clinical trials. However, greater effort must be taken to develop approaches that will lead towards a curing solution to COPD patients.   ADDITIONAL RESEARCH

Stem cell therapy in chronic obstructive pulmonary disease. How far is it to the clinic?

https://www.ncbi.nlm.nih.gov/pubmed/30245915 

  • Previous studies suggest that cell-based therapies and novel bioengineering approaches may be potential therapeutic strategies for lung repair and remodelling. In this paper, we review the current evidence of stem cell therapy in COPD.

The clinical use of regenerative therapy in COPD.

https://www.ncbi.nlm.nih.gov/pubmed/25548520  

  • Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease.

Concise Review: Clinical Prospects for Treating Chronic Obstructive Pulmonary Disease with Regenerative Approaches

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659729/ 

  • Cell therapies using various stem cells have been extensively evaluated. The lung is one of the easiest organs in which to instill exogenous cells because cells can be applied through both the airway and circulation. In addition, most of the intravenously instilled cells are trapped within the pulmonary circulation; therefore, the efficacy of cell delivery is naturally high.
  • Mesenchymal stem cells (MSCs) are the most extensively evaluated candidates for clinical cell-based therapy. Many clinical trials using MSCs have been registered and are ongoing. Autologous MSCs are easily isolated from the bone marrow and other tissues. MSCs are expected to reduce inflammation and promote the repair process. These beneficial effects are thought to be based on the ability of MSCs to modulate the immune system and their capacity to produce growth factors and cytokines [49], such as keratinocyte growth factor, HGF, and prostaglandin E2.
  • Because of these anti-inflammatory effects, a phase II clinical trial using MSCs has been performed in moderate and severe COPD patients [50]. The trial successfully demonstrated the safety of cell therapies using MSCs and some reduction in the inflammatory response in COPD patients but did not show any beneficial effects on lung function. Additional studies, especially in early-stage COPD patients, are needed.

Stem cell therapy: the great promise in lung disease.

https://www.ncbi.nlm.nih.gov/pubmed/19124369

  • The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that bone marrow progenitor cells contribute to repair and remodeling of lung in animal models of progressive pulmonary hypertension. Therefore, lung stem cell biology may provide novel approaches to therapy and could represent a great promise for the future of molecular medicine. In fact, several diseases can be slowed or even blocked by stem cell transplantation.

Current Status of Stem Cells and Regenerative Medicine in Lung Biology and Diseases

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208500/

  • Exciting progress in each of these areas provides further understanding of lung biology and repair after lung injury and further a sound scientific basis for therapeutic use of cell therapies and bioengineering approaches in treatment of lung diseases

Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730369/ 

  • Much study, so far, has been done to evaluate MSC-mediated cell therapy in various lung conditions, albeit mostly in animal models. In this case, it is important to note that the bulk of studies suggest the infused MSCs exhibits reparative/healing effects mostly through paracrine or immunomodulatory effects on recipient lung tissue, but not by engraftment Thus, it is imperative to view MSC therapy as cell-based immunomodulatory therapy rather than as attempts to regenerate or reconstitute lung tissues [6]. Nonetheless, much effort has been taken to date to understand the molecular mechanisms of lung development, disease dynamics and its regenerative process.

Endogenous and exogenous stem cells: a role in lung repair and use in airway tissue engineering and transplantation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004872/ 

  • Human amniotic fluid SCs (hAFSCs) and umbilical blood cord (UBC)-derived SCs are new cell resources for lung regeneration. Human umbilical cord blood is a promising source for human MSCs Recent advances in airway tissue engineering provide a good opportunity for the treatment of a wide range of lung defects. In addition to the respiratory failure cases mentioned above, SC-based therapies show great potential for new clinical applications against acute respiratory distress syndrome [72], asthma [73], and bronchopulmonary dysplasia [74]. At present, the therapeutic potential of SCs is intensively assessed in rodent models of these diseases, with the possibility of proceeding to clinical trials

Adult stem cells for chronic lung diseases

https://onlinelibrary.wiley.com/doi/full/10.1111/resp.12112 

  • Conclusion: As a self‐repair mechanism, living organisms have stem cells that are attracted to sites of injury. Chronic injury as well as ageing could exhaust and impair stem cell reparative capacity as well as diminish number of available stem cells. The mechanism(s) by which alterations in the homeostasis of stem cells pools are involved in the pathogenesis of chronic lung diseases is unknown. If stem cell exhaustion and ageing is the cause of morbid states, stem cell‐based therapies will be able to prevent and treat them. Restoration of stem cells has shown promising therapeutic benefits for certain lung pathologies. Particularly, the immunomodulatory capacity of B‐MSC has been shown to be beneficial for lung diseases with exacerbated inflammatory responses. However, a generalized use of B‐MSC in chronic lung diseases must be considered with caution, and careful studies are still required to establish safety and efficacy of such use.

Lung regeneration using amniotic fluid mesenchymal stem cells

https://www.tandfonline.com/doi/abs/10.1080/21691401.2017.1337023?journalCode=ianb20 

  • In this review, we give an update on the use of amniotic fluid mesenchymal stem cells (AFMSCs) as an optimal source for lungs scaffold re-cellularization, due to their limitless accessibility and possibility for proliferation and differentiation. Further studies will be required in tissue engineering (TE) and regenerative medicine (RM), especially shifting our focus towards AFMSCs as a cell source for this regeneration.

Stem cell therapy for lung diseases: From fundamental aspects to clinical applications.

https://www.ncbi.nlm.nih.gov/pubmed/30084809 

  • This review summarizes the recent advances in stem cell treatments and the research efforts conducted through the application of stem cell therapy for respiratory system diseases. In particular, researchers have used animal models to gather data about treating lung injury by stem cell transplantation. This review concentrated on the findings about route, timing and adjustment of cell transplantation dose, optimum stem cell type selection and potency marker of cells as therapeutic agents.

Adult stem cells in the treatment of autoimmune diseases

https://academic.oup.com/rheumatology/article/45/10/1187/2255946 

  • The past decade has seen the introduction of many agents, especially biologics, which have allowed a more successful control of AD manifestations. However, the elusive aim of tolerance induction has not yet been achieved. It could be that through harnessing the complex and multifaceted potential of cellular-based therapies, especially HSCT, a ‘resetting‘ of auto-aggressive immune reactions while maintaining protective immunity will be possible. In addition, the anti-proliferative and immunomodulatory properties of MSCs combined with their immunological privilege and seemingly low toxicity may offer a new strategy for controlling and protecting vital organs from inflammatory, destructive autoimmune reactions.

Treatment of severe autoimmune disease by stem-cell transplantation

https://www.nature.com/articles/nature03728 

  • Transplantation of haematopoietic stem cells — cells capable of self renewing and reconstituting all types of blood cell — can treat numerous lethal diseases, including leukaemias and lymphomas. It may now be applicable for the treatment of severe autoimmune diseases, such as therapy-resistant rheumatoid arthritis and multiple sclerosis. Studies in animal models show that the transfer of haematopoietic stem cells can reverse autoimmunity, and several mechanistic pathways may explain this phenomenon.

A lethal autoimmune disease succumbs to stem cells

https://www.nature.com/articles/d41586-018-00078-6 

  • The results are consistent with two previous stem-cell trials, and should help to establish stem-cell transplants as a standard treatment for individuals with severe scleroderma, according to the researchers.

Human Umbilical Cord Blood Stem Cells Infusion in Spinal Cord Injury: Engraftment and Beneficial Influence on Behavior

https://www.liebertpub.com/doi/abs/10.1089/152581603322023007 

  • Open-field test scores of spinal cord injured rats treated with human cord blood at 5 days were significantly improved as compared to scores of rats similarly injured but treated at day 1 as well as the otherwise untreated injured group. The results suggest that cord blood stem cells are beneficial in reversing the behavioral effects of spinal cord injury, even when infused 5 days after injury. Human cord blood-derived cells were observed in injured areas, but not in non-injured areas, of rat spinal cords, and were never seen in corresponding areas of spinal cord of non-injured animals. The results are consistent with the hypothesis that cord blood-derived stem cells migrate to and participate in the healing of neurological defects caused by traumatic assault.

Bone Marrow Mononuclear Cells Have Neurovascular Tropism and Improve Diabetic Neuropathy

https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.87 

  • In this study, we showed that the transplantation of BMNCs restored the vascularity and function of diabetic nerves, supporting the hypothesis that neural vascularity is pathophysiologically associated with the development and reversal of DN

Multipotent Stem Cells from Umbilical Cord: Cord Is Richer than Blood!

https://stemcellsjournals.onlinelibrary.wiley.com/doi/10.1634/stemcells.2007-0381 

  • Despite the advantages of HSC from UCB in hematopoietic reconstitution [13, 14–15], results from the present study demonstrated that UC, and not UCB, is the best choice for isolating MSCs for future applications. Until very recently, BM has been considered the main source of MSCs. Panepucci et al. demonstrated that MSCs derived from UC and BM are highly similar at the transcriptional level, reinforcing the usefulness of UC from neonates [34].

Life‐Sparing Effect of Human Cord Blood‐Mesenchymal Stem Cells in Experimental Acute Kidney Injury†

https://stemcellsjournals.onlinelibrary.wiley.com/doi/10.1002/stem.293

  • CONCLUSION In conclusion, in a murine model of AKI, hCB‐MSC treatment promotes kidney regeneration and prolongs survival better than any other cellular approach attempted so far. These effects appear to be mediated by a paracrine action of hCB‐MSCs on tubular cells involving lowering oxidative stress, apoptosis, and inflammation. These data indicate that hCB‐MSCs have to be considered as one possible future option for cellular therapy of AKI in humans.

Human Umbilical Cord‐Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia

https://stemcellsjournals.onlinelibrary.wiley.com/doi/10.5966/sctm.2015-0298 

  • Conclusion This is the first study to provide evidence that intracoronary delivery combined with multiple intravenous infusions of UC‐MSCs improves LV function, perfusion, and remodeling in a large animal model of chronic myocardial ischemia. In the present study, we observed neither tumor nor teratoma formation in human UC‐MSC‐transplanted animals, and no sustained ventricular arrhythmia or anaphylaxis was observed. Because these cells can be isolated from medical waste, expanded, banked, and administered to patients at any time without immunological rejection, human UC‐MSCs might be an ideal cell source for cardiac cell therapy and hold promise as an off‐the‐shelf product.

Intravenous Infusion of Umbilical Cord Blood‐Derived Mesenchymal Stem Cells in Rheumatoid Arthritis: A Phase Ia Clinical Trial

https://stemcellsjournals.onlinelibrary.wiley.com/doi/10.1002/sctm.18-0031 

  • Conclusion This is the first phase Ia study of RA patients that evaluated the safety and tolerability of a single intravenous infusion with hUCB‐MSCs and with cell numbers of up to 1 × 108, revealing an acceptable safety profile. Conclusions regarding efficacy in phase I trials are limited, and although evaluation of disease activity was not the primary objective of this study, a single infusion of hUCB‐MSCs effectively reduced the mean DAS28 at week 4. Considering favorable safety profiles, intravenous infusion of hUCB‐MSCs may constitute a therapeutic option for patients with RA, who are refractory to or intolerant of MTX. There is a wide array of opportunities for future clinical studies with different hUCB‐MSC infusion strategies in which safety profiles should be carefully monitored and outcome measures further refined for optimized effectiveness evaluations.

Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis.

https://www.ncbi.nlm.nih.gov/pubmed/30290717 

  • Proteinuria levels improved dramatically during the 1st month after treatment and the ameliorations were sustained throughout the follow-up period. SLEDAI scores revealed early, durable, and substantial remissions that were complete for two patients and partial for the third patient and that permitted medication doses to be reduced 50-90%. These favourable outcomes support completion of the randomized and controlled MSC trial for SLE.

Mesenchymal Stromal Cells Based Therapy in Systemic Sclerosis: Rational and Challenges

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146027/ 

  • The ability of MSCs to positively influence processes such as immunosuppression, angiogenesis and inflammation generated a lot of interest and enthusiasm from clinicians and researchers alike. It is apparent that many questions remain unanswered, however what is becoming clear is that MSCs-based therapy should considered as a safe and potentially efficient therapeutic option in the management of advanced stage of SSc.

The Use of Human Mesenchymal Stem Cells as Therapeutic Agents for the in vivo Treatment of Immune-Related Diseases: A Systematic Review

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141714/ 

  • In this systematic review, the treatment of many types of immune-related diseases was conducted through the administration of hMSCs. Positive results were usually reported and attributed to the paracrine effects of molecules secreted by hMSCs on immune cells. In conclusion, despite the need for further studies, the treatment of immune-related diseases through the administration of hMSCs is progressively ceasing being only a promising possibility and becoming a reality.

Mesenchymal stem cells alleviate experimental autoimmune cholangitis through immunosuppression and cytoprotective function mediated by galectin-9

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142687/ 

  • In summary, the present study shows that UC-MSCs exert profound inhibitory effects on inflammatory responses to alleviate liver injury in experimental autoimmune cholangitis mice. Furthermore, UC-MSCs inhibit Th1 and Th17 cell responses as well as aberrant chemokine activities through Gal-9–mediated immunosuppression. Additionally, the induction of Gal-9 in UC-MSCs is mediated by the STAT and JNK signaling pathways. Our results provide novel insights into the clinical application of UC-MSCs in the treatment of PBC.

The Beneficial Effect of Human Amnion Mesenchymal Cells in Inhibition of Inflammation and Induction of Neuronal Repair in EAE Mice

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035808/ 

  • Recently, accumulating evidence showed that MSCs from different origins, including adipose-derived, bone marrow-derived, and umbilical cord-derived, could attenuate the disease progression in EAE animal models [27–29]. Furthermore, autologous bone marrow-derived MSCs transplantation and allogeneic umbilical cord-derived MSCs transplantation for the treatment of MS have been proved safe and effective in clinical trials, which showed that treatment improved the course of the disease, reduced the inflammatory response, and promoted neuroprotection

TGF-β and mesenchymal stromal cells in regenerative medicine, autoimmunity and cancer.

https://www.ncbi.nlm.nih.gov/pubmed/29954665 

  • Multipotent mesenchymal stromal cells (MSCs) represent a promising cell-based therapy in regenerative medicine and for the treatment of inflammatory/autoimmune diseases. Importantly, MSCs have emerged as an important contributor to the tumor stroma with both pro- and anti-tumorigenic effects

Modulation of autophagy as new approach in mesenchymal stem cell-based therapy.

https://www.ncbi.nlm.nih.gov/pubmed/29787987

  • Here, we review the current literature describing mechanisms by which modulation of autophagy strengthens pro-angiogenic and immunosuppressive characteristics of MSCs in animal models of multiple sclerosis, osteoporosis, diabetic limb ischemia, myocardial infarction, acute graft-versus-host disease, kidney and liver diseases. Obtained results suggest that modulation of autophagy in MSCs may represent a new therapeutic approach that could enhance efficacy of MSCs in the treatment of ischemic and autoimmune diseases.

Therapeutic Applications of Mesenchymal Stem Cells for Systemic Lupus Erythematosus.

https://www.ncbi.nlm.nih.gov/pubmed/29767288 

  • Mesenchymal stem cells (MSCs) have been intensively studied and applied in regenerative medicine and tissue engineering. Recently, their immune modulation functions make them as attractive potential approaches for autoimmune disease treatment. Systemic lupus erythematosus (SLE) is one type of chronic autoimmune diseases with multi-organ damaged by the immune system. Although current available treatments are effective for some patients, others are refractory for these therapies. The immuno-modulatory and regenerative characteristics of MSCs make them as one promising candidate for treating SLE.

Cell therapies for refractory rheumatoid arthritis.

https://www.ncbi.nlm.nih.gov/pubmed/29745893 

  • Recently, cell-based therapies have become the focus, attracting more attention due to their potential for remission induction. Several immune-regulatory cell types, such as haematopoietic stem cells, mesenchymal stem cells and regulatory T cells have been defined as novel targets.

Mesenchymal stem cell transplantation in systemic lupus erythematous, a mesenchymal stem cell disorder.

https://www.ncbi.nlm.nih.gov/pubmed/29631514 

  • MSCs from SLE patients have demonstrated defects such as aberrant cytokine production. Moreover, impaired phenotype, growth and immunomodulatory functions of MSCs from patients with SLE in comparison to healthy controls have been reported. Therefore, it is hypothesized that SLE is potentially an MSC-mediated disease and, as a result, allogeneic rather than autologous MSC transplantation can be argued to be a potentially advantageous therapy for patients with SLE.

Hematopoietic and mesenchymal stem cell transplantation for severe and refractory systemic lupus erythematosus.

https://www.ncbi.nlm.nih.gov/pubmed/23770628 

  • Recently, growing evidence suggests that the functions of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are disrupted in SLE pathology. And HSC or MSC transplantation (HSCT/MSCT) can offer an effective and safe therapy for the severe SLE patients, resulting in disease clinical remission and improvement of organ dysfunction.

The protective effects of human umbilical cord mesenchymal stem cells on damaged ovarian function: A comparative study.

https://www.ncbi.nlm.nih.gov/pubmed/27464625

  • A higher level of expression of anti-apoptotic and antioxidant enzymes was noted in the ovaries of groups treated with hUCMSCs. These parameters were enhanced more when mice were treated with hUCMSCs for 1 month than when they treated with hUCMSCs for 2 weeks. IV was better able to restore ovarian function than MI. These results suggest that both methods of transplantation may improve ovarian function and that IV transplantation of hUCMSCs can significantly improve ovarian function and structural parameters more than MI transplantation of hUCMSCs can.

Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism.

https://www.ncbi.nlm.nih.gov/pubmed/28279229 

  • CONCLUSIONS: Our results suggest that hUCMSCs can promote ovarian expression of HGF, VEGF, and IGF-1 through secreting those cytokines, resulting in improving ovarian reserve function and withstanding ovarian senescence.

Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5273808/ 

  • BACKGROUND: Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model.
  • CONCLUSIONS: Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium.

Long term effect and safety of Wharton’s jelly-derived mesenchymal stem cells on type 2 diabetes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997981/

  • In conclusion, the findings of the present study suggested that WJ-MSC infusion may effectively ameliorate hyperglycemia, improve islet β-cell function and reduce the incidence of diabetic complications over a sustained period of time. Despite the fact that WJ-MSC infusion does not appear to attenuate insulin resistance, WJ-MSC infusion may have therapeutic potential as a novel agent for the treatment of T2DM.

Long term effect and safety of Wharton’s jelly-derived mesenchymal stem cells on type 2 diabetes

https://www.researchgate.net/publication/305677302_Long_term_effect_and_safety_of_Wharton’s_jelly-derived_mesenchymal_stem_cells_on_type_2_diabetes

  • Cellular therapies offer novel opportunities for the treatment of type 2 diabetes mellitus (T2DM). The present study evaluated the long-term efficacy and safety of infusion of Wharton’s jelly-derived mesenchymal stem cells (WJ-MSC) on T2DM. A total of 61 patients with T2DM were randomly divided into two groups on the basis of basal therapy; patients in group I were administered WJ-MSC intravenous infusion twice, with a four-week interval, and patients in group II were treated with normal saline as control. During the 36-month follow-up period, the occurrence of any adverse effects and the results of clinical and laboratory examinations were recorded and evaluated. The lack of acute or chronic adverse effects in group I was consistent with group II.. Blood glucose, glycosylated hemoglobin, C-peptide, homeostasis model assessment of pancreatic islet β-cell function and incidence of diabetic complications in group I were significantly improved, as compared with group II during the 36-month follow-up. The results of the present study demonstrated that infusion of WJ-MSC improved the function of islet β-cells and reduced the incidence of diabetic complications, although the precise mechanisms are yet to be elucidated. The infusion of WJ-MSC may be an effective option for the treatment of patients with type 2 diabetes.

Mesenchymal stem cells in tissue repair.

https://www.ncbi.nlm.nih.gov/pubmed/24027567

  • Mesenchymal stem cells have become a major focus for a potential resource in therapeutic cell-based therapies. MSCs are multipotent cells derived from stromal tissue, which have the capacity to differentiate into mesodermal and endodermal types of cells. Not only do MSCs have the capacity to differentiate into different types of cells depending on the tissue matrix, they also actively contribute to their milieu by secreting soluble products that actively participate in MSC and surrounding cell phenotype.

Mesenchymal stem cells from human umbilical cord express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis.

https://www.ncbi.nlm.nih.gov/pubmed/23991127

  • Our results confirmed that WJ-MSCs secreted highly levels of CXCL5 compared with BM-MSCs.

Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis.

https://www.ncbi.nlm.nih.gov/pubmed/21080925

  • In conclusion, human UC-MSCs suppressed the various inflammatory effects of FLSs and T cells of RA in vitro, and attenuated the development of CIA in vivo, strongly suggesting that UC-MSCs might be a therapeutic strategy in RA. In addition, the immunosuppressive activitiy of UC-MSCs could be prolonged by the participation of Tregs.

Stem cell delivery of therapies for brain disorders

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106911/

  • MSCs have the potential as cellular vehicles for drugs and other molecules to treat patients with neural diseases such as GBM, AD, PD, TBI and other neuropathologies for which limited treatment options exist. When considering the limitations of current methods of drug delivery to the brain, MSCs have the potential to become a safe cellular delivery vehicle containing a prodrug as well as ectopically expressed genes for targeted delivery. The affinity for MSCs to migrate to the brain combined with the relative ease for expanded MSCs make them attractive for gene and drug delivery.

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