For your convenience, Research articles are organized in the following categories.
UMBILICAL CORD / WHARTON’S JELLY
Immunosuppressive properties of mesenchymal stromal cells derived from amnion, placenta, Wharton’s jelly and umbilical cord.
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
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.
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. file:///C:/Users/don/Downloads/536-Article%20Text-590-1-10-20151018.pdf
Therefore UC-MSCs may have an extended culture capacity compared to BM-MSCs, specifically greater than 20 passages. In fact, it has been shown that UCMSCs are transitional between embryonic and adult stem cells and possess higher proliferation and differentiation rate than BM-MSCs and therefore can be helpful in research and clinical applications.
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.
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.
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.
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.
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. NEUROPATHY
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.
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
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.
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. ORTHOPEDIC CONDITIONS / SPORTS INJURIES
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.
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 , , , , , , . 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 , 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 , ,  and justify the use of WJSCs in cartilage regeneration procedures.
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.
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.
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. 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 “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 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
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.
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
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.
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)
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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 . 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 . 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 . 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 . 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.
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.
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.
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.
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.
Article: Autologous Cellular Therapy and its Effects on COPD: A Pilot Study
Article: COPD Improves with Stem Cell Therapy
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
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.
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.
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 , 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 . 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.
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.
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
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 . Nonetheless, much effort has been taken to date to understand the molecular mechanisms of lung development, disease dynamics and its regenerative process.
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 , asthma , and bronchopulmonary dysplasia . At present, the therapeutic potential of SCs is intensively assessed in rodent models of these diseases, with the possibility of proceeding to clinical trials
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.
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.
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.
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.
In conclusion, the systemic infusion of autologous stem cells described here offers promise for better management of a wide spectrum of autoimmune diseases, independent on patient’s age.
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.
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.
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. file:///C:/Users/don/Downloads/470983%20(1).pdf NEUROPATHY
It is important to underline that one of the main aspects concerning stem cells usage is both their fast onset and long lasting effect on pain relief; a single administration of cells is in fact able to induce an antiallodynic and antihyperalgesic effect which persists for long time, as it is still present up to 90 days after injection . Generally, the conventional  and the newer pharmacological strategies [55, 56] for neuropathic pain treatment need a chronic treatment to be
effective. The analgesic success of the commonly available drugs is often limited by side effects that appear increasing the administration dose or by the development of tolerance . Moreover, in order to successfully approach this type of pain, patients often are treated with a combination of drugs with different mechanisms of action, increasing the risk of drug interaction and often reducing patient’s compliance . A more long lasting effect for some type of neuropathic pain such as low back pain or disk herniation can eventually be achieved by surgical approaches or epidural treatment, obviously exposing the patients to all the risks of the surgery. The clamorous effect of stem cells on pain relief in the preclinical tests may be related to their capacity to not only control pain as a symptom, but to act as disease modifier on the mechanisms at the basis of the development and maintenance of pain condition, for example, modulating the neuroimmune component which plays a relevant role in neuropathic pain.
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
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 .
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.
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.
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.
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.
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.
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.
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.
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
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
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.
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.
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.
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.
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.
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.
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.
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.
At Virginia Advanced Medical (the “Company” or “We”), we respect your privacy and are committed to protecting it through our compliance with this policy.
This policy describes the types of information we may collect from you or that you may provide when you visit this website (our “Website”) and our practices for collecting, using, maintaining, protecting and disclosing that information.
This policy applies to information we collect:
- On this Website.
- In e-mail, text and other electronic messages between you and this Website.
- Through mobile and desktop applications you download from this Website, which provide dedicated non-browser-based interaction between you and this Website.
- When you interact with our advertising and applications on third-party websites and services, if those applications or advertising include links to this policy.
It does not apply to information collected by:
- us offline or through any other means, including on any other website operated by Company or any third party (including our affiliates and subsidiaries); or
- any third party (including our affiliates and subsidiaries), including through any application or content (including advertising) that may link to or be accessible from or on the Website.
Children Under the Age of 13
Our Website is not intended for children under 13 years of age. No one under age 13 may provide any personal information to or on the Website. We do not knowingly collect personal information from children under 13. If you are under 13, do not use or provide any information on this Website or on or through any of its features/register on the Website, make any purchases through the Website, use any of the interactive or public comment features of this Website or provide any information about yourself to us, including your name, address, telephone number, e-mail address or any screen name or user name you may use. If we learn we have collected or received personal information from a child under 13 without verification of parental consent, we will delete that information. If you believe we might have any information from or about a child under 13, please contact us via our contact us link.
Information We Collect About You and How We Collect It
We collect several types of information from and about users of our Website, including information:
- by which you may be personally identified, such as name, postal address, e-mail address, telephone number or ANY OTHER INFORMATION THE WEBSITE COLLECTS THAT IS DEFINED AS PERSONAL OR PERSONALLY IDENTIFIABLE INFORMATION UNDER AN APPLICABLE LAW (“personal information”);
- that is about you but individually does not identify you, and/or
- about your internet connection, the equipment you use to access our Website and usage details.
We collect this information:
- Directly from you when you provide it to us.
- Automatically as you navigate through the site. Information collected automatically may include usage details, IP addresses and information collected through cookies, web beacons and other tracking technologies.
- From third parties, for example, our business partners.
Information You Provide to Us.
The information we collect on or through our Website may include:
- Information that you provide by filling in forms on our Website. This includes information provided at the time of registering to use our Website, subscribing to our service, posting material or requesting further services. We may also ask you for information when you report a problem with our Website.
- Records and copies of your correspondence (including e-mail addresses), if you contact us.
- Your responses to surveys that we might ask you to complete for research purposes.
- Details of transactions you carry out through our Website and of the fulfillment of your orders. You may be required to provide financial information before placing an order through our Website.
- Your search queries on the Website.
You also may provide information to be published or displayed (hereinafter, “posted”) on public areas of the Website, or transmitted to other users of the Website or third parties (collectively, “User Contributions”). Your User Contributions are posted on and transmitted to others at your own risk. Although we limit access to certain pages/you may set certain privacy settings for such information by logging into your account profile, please be aware that no security measures are perfect or impenetrable. Additionally, we cannot control the actions of other users of the Website with whom you may choose to share your User Contributions. Therefore, we cannot and do not guarantee that your User Contributions will not be viewed by unauthorized persons.
Information We Collect Through Automatic Data Collection Technologies.
As you navigate through and interact with our Website, we may use automatic data collection technologies to collect certain information about your equipment, browsing actions and patterns, including:
- Details of your visits to our Website, including traffic data, location data, and other communication data and the resources that you access and use on the Website.
- Information about your computer and internet connection, including your IP address, operating system and browser type.
We also may use these technologies to collect information about your online activities over time and across third-party websites or other online services (behavioral tracking). The information we collect automatically is statistical data and does not include personal information, but we may maintain it or associate it with personal information we collect in other ways or receive from third parties. It helps us to improve our Website and to deliver a better and more personalized service, including by enabling us to:
- Estimate our audience size and usage patterns.
- Store information about your preferences, allowing us to customize our Website according to your individual interests.
- Speed up your searches.
- Recognize you when you return to our Website.
The technologies we use for this automatic data collection may include:
- Flash Cookies. Certain features of our Website may use local stored objects (or Flash cookies) to collect and store information about your preferences and navigation to, from and on our Website. Flash cookies are not managed by the same browser settings as are used for browser cookies.
- Web Beacons. Pages of our the Website may contain small electronic files known as web beacons (also referred to as clear gifs. pixel tags and single-pixel gifs) that permit the Company, for example, to count users who have visited those pages or opened an e-mail and for other related website statistics (for example, recording the popularity of certain website content and verifying system and server integrity).
We do not collect personal Information automatically, but we may tie this information to personal information about you that we collect from other sources or you provide to us.
We do not control these third parties’ tracking technologies or how they may be used. If you have any questions about an advertisement or other targeted content, you should contact the responsible provider directly.
How We Use Your Information
We use information that we collect about you or that you provide to us, including any personal information:
- To present our Website and its contents to you.
- To provide you with information, products or services that you request from us.
- To provide you with information about our services
- To provide you with notices about your account/subscription, including expiration and renewal notices.
- To carry out our obligations and enforce our rights arising from any contracts entered into between you and us, including for billing and collection.
- To notify you about changes to our Website or any products or services we offer or provide though it.
- To allow you to participate in interactive features on our Website.
- In any other way we may describe when you provide the information.
- To fulfill any purpose for which you provide it.
- For any other purpose with your consent.
We may use the information we have collected from you to enable us to display advertisements to our advertisers’ target audiences. Even though we do not disclose your personal information for these purposes without your consent, if you click on or otherwise interact with an advertisement, the advertiser may assume that you meet its target criteria.
Disclosure of Your Information
We may disclose aggregated information about our users, and information that does not identify any individual, without restriction.
- To our subsidiaries and affiliates.
- To contractors, service providers and other third parties we use to support our business and who are bound by contractual obligations to keep personal information confidential and use it only for the purposes for which we disclose it to them.
- To a buyer or other successor in the event of a merger, divestiture, restructuring, reorganization, dissolution or other sale or transfer of some or all of the Company’s assets, whether as a going concern or as part of bankruptcy, liquidation or similar proceeding, in which personal information held by the Company about our Website users is among the assets transferred.
- To third parties to market their products or services to you if you have consented to these disclosures. We contractually require these third parties to keep personal information confidential and use it only for the purposes for which we disclose it to them.
- To fulfill the purpose for which you provide it. For example, if you give us an e-mail address to use the “e-mail a friend” feature of our Website, we will transmit the contents of that e-mail and your e-mail address to the recipients.
- For any other purpose disclosed by us when you provide the information.
- With your consent.
We may also disclose your personal information:
- To comply with any court order, law or legal process, including to respond to any government or regulatory request.
- If we believe disclosure is necessary or appropriate to protect the rights, property, or safety of the Company, our customers or others. This includes exchanging information with other companies and organizations for the purposes of fraud protection and credit risk reduction.
Choices About How We Use and Disclose Your Information
We strive to provide you with choices regarding the personal information you provide to us. We have created mechanisms to provide you with the following control over your information:
- We do not control third parties’ collection or use of your information to serve interest-based advertising. However these third parties may provide you with ways to choose not to have your information collected or used in this way. You can opt out of receiving targeted ads from members of the Network Advertising Initiative (“NAI”) on the NAI’s website.
Accessing and Correcting Your Information
You may send us an e-mail via our contact link to request access to, correct or delete any personal information that you have provided to us. We cannot delete your personal information except by also deleting your user account. We may not accommodate a request to change information if we believe the change would violate any law or legal requirement or cause the information to be incorrect.
Your California Privacy Rights
California Civil Code Section § 1798.83 permits users of our Website that are California residents to request certain information regarding our disclosure of personal information to third parties for their direct marketing purposes. To make such a request, please contact us via the Contact Us link.
We have implemented measures designed to secure your personal information from accidental loss and from unauthorized access, use, alteration and disclosure
The safety and security of your information also depends on you. Where we have given you (or where you have chosen) a password for access to certain parts of our Website, you are responsible for keeping this password confidential. We ask you not to share your password with anyone.
Unfortunately, the transmission of information via the internet is not completely secure. Although we do our best to protect your personal information, we cannot guarantee the security of your personal information transmitted to our Website. Any transmission of personal information is at your own risk. We are not responsible for circumvention of any privacy settings or security measures contained on the Website.
Thank You for Visiting the Website.