Human umbilical cord mesenchymal stem cells (HUC-MSCs) present in the umbilical cord tissue are self-renewing and multipotent. They can renew themselves continuously and, under certain conditions, differentiate into one or more cell types constituting human tissues and organs. HUC-MSCs differentiate, among others, into osteoblasts, chondrocytes, and adipocytes and have the ability to secrete cytokines. The possibility of noninvasive harvesting and low immunogenicity of HUC-MSCs give them a unique advantage in clinical applications. In recent years, HUC-MSCs have been widely used in clinical practice, and some progress has been made in their use for therapeutic purposes. This article describes two aspects of the clinical therapeutic effects of HUC-MSCs. On the one hand, it explains the benefits and mechanisms of HUC-MSC treatment in various diseases. On the other hand, it summarizes the results of basic research on HUC-MSCs related to clinical applications. The first part of this review highlights several functions of HUC-MSCs that are critical for their therapeutic properties: differentiation into terminal cells, immune regulation, paracrine effects, anti-inflammatory effects, anti-fibrotic effects, and regulating non-coding RNA. These characteristics of HUC-MSCs are discussed in the context of diabetes and its complications, liver disease, systemic lupus erythematosus, arthritis, brain injury and cerebrovascular diseases, heart diseases, spinal cord injury, respiratory diseases, viral infections, and other diseases. The second part emphasizes the need to establish an HUC-MSC cell bank, discusses tumorigenicity of HUC-MSCs and the characteristics of different in vitro generations of these cells in the treatment of diseases, and provides technical and theoretical support for the clinical applications of HUC-MSCs. HUC-MSCs can treat a variety of diseases clinically and have achieved good therapeutic effects, and the development of HUC-MSC assistive technology has laid the foundation for its clinical application.

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What is the impact of human umbilical cord mesenchymal stem cell transplantation on clinical treatment

As part of the TACTICS (Transnational Alliance for Regenerative Therapies in Cardiovascular Syndromes) series to enhance regenerative medicine, here, we discuss the role of preclinical studies designed to advance stem cell therapies for cardiovascular disease. The quality of this research has improved over the past 10 to 15 years and overall indicates that cell therapy promotes cardiac repair. However, many issues remain, including inability to provide complete cardiac recovery. Recent studies question the need for intact cells suggesting that harnessing what the cells release is the solution. Our contribution describes important breakthroughs and current directions in a cell-based approach to alleviating cardiovascular disease.

Preclinical Studies of Stem Cell Therapy for Heart Disease.

Requirment of activation of the extracellular signal-regulated kinase cascade in myocardial cell hypertrophy

Mesenchymal stem cells (MSCs) can be recruited to damaged tissues directly for regeneration. Exosomes, acting as an important ingredient of MSCs-involved intercellular communication through paracrine actions, also play significant roles in tissue damage repair and have a prospect of potential clinical application. It is generally recognized that MSC-derived exosomes (MSC-exosomes) enhance tissue regeneration and repair through reducing inflammatory responses, promoting proliferation, inhibiting apoptosis and facilitating angiogenesis. This review summarizes the positive effects of human umbilical cord mesenchymal stem cells (hucMSCs) and hucMSC-derived exosomes (hucMSC-exosomes) on tissue damage and the specific mechanisms of repair action.

Human umbilical cord mesenchymal stem cells and exosomes: bioactive ways of tissue injury repair.

Umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have recently gained considerable attention in the field of regenerative medicine Their high proliferation rate, differentiation ability into various cell lineages, easy collection procedure, immuno-privileged status, nontumorigenic properties along with minor ethical issues make them an ideal approach for tissue repair Besides, the number of WJ-MSCs in the umbilical cord samples is high as compared to other sources Because of these properties, WJ-MSCs have rapidly advanced into clinical trials for the treatment of a wide range of disorders Therefore, this paper summarized the current preclinical and clinical studies performed to investigate the regenerative potential of WJ-MSCs in neural, myocardial, skin, liver, kidney, cartilage, bone, muscle, and other tissue injuries

Regenerative potential of Wharton's jelly-derived mesenchymal stem cells: A new horizon of stem cell therapy.

Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord‑derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin‑induced rat model of DCM. Male Lewis rats (aged 8‑weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1x106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle‑injected and negative control rats. Myosin injections in rats (vehicle group and experimental group) for 28 days led to severe fibrosis and significant deterioration of cardiac function indicative of DCM. HuMSC treatment reduced fibrosis as determined by Masson's staining of collagen deposits, as well as quantification of molecular markers of myocardial fibrosis such as collagen I/III, profibrotic factors transforming growth factor‑β1 (TGF‑β1), tumor necrosis factor‑α (TNF‑α), and connective tissue growth factor (CTGF). HuMSC treatment restored cardiac function as observed using echocardiography. In addition, western blot analysis indicated that HuMSC injections in DCM rats inhibited the expression of TNF‑α, extracellular‑signal regulated kinase 1/2 (ERK1/2) and TGF‑β1, which is a master switch for inducing myocardial fibrosis. These findings suggested that HuMSC injections attenuated myocardial fibrosis and dysfunction in a rat model of DCM, likely by inhibiting TNF‑α and the TGF‑β1/ERK1/2 fibrosis pathways. Therefore, HuMSC treatment may represent a potential therapeutic method for treatment of DCM.

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Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF‑α and TGF‑β1/ERK1/2 signaling pathways

Acute myocarditis is a non-ischemic inflammatory disease of the myocardium, and there is currently no standard treatment. Mesenchymal stem cells (MSCs) can alleviate myosin‑induced myocarditis; however, the mechanism has not been clearly elucidated. In the present study, the authors investigated the ability of human umbilical cordMSCs (HuMSCs) to attenuate myocardial injury and dysfunction during the acute phase of experimental myocarditis. Male Lewis rats (aged 8 weeks) were injected with porcine myosin to induce myocarditis. Cultured HuMSCs (1x106 cells/rat) were intravenously injected 10 days following myosin injection. A total of 3 weeks following injection, this resulted in severe inflammation and significant deterioration of cardiac function. HuMSC transplantation attenuated infiltration of inflammatory cells and adverse cardiac remodeling, as well as reduced cardiomyocyte apoptosis. Furthermore, it was identified that HuMSC transplantation suppressed endoplasmic reticulum stress and extracellular signal‑regulated kinase (ERK)1/2 signaling in experimental autoimmune myocarditis (EAM). The reduced number of TUNEL‑positive apoptotic cells in myocardial sections from HuMSC‑treated EAM rats compared with control demonstrates HuMSCs' anti‑apoptotic function. Based on these data, the author suggested that treatment with HuMSCs inhibits myocardial apoptosis in EAM rats, ultimately protecting them from myocardial damage. The conclusion demonstrated that HuMSC transplantation attenuates myocardial injury and dysfunction in a rat model of acute myocarditis, potentially via regulation of ER stress, ERK1/2 signaling and induction of cardiomyocyte apoptosis.

/pdf/human-umbilical-cord-mesenchymal-stem-cells-alleviate-acute-3x4kvs7xft.pdf

Human umbilical cord mesenchymal stem cells alleviate acute myocarditis by modulating endoplasmic reticulum stress and extracellular signal regulated 1/2-mediated apoptosis.

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Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF‑α and TGF‑β1/ERK1/2 signaling pathways

Human umbilical cord mesenchymal stem cells alleviate acute myocarditis by modulating endoplasmic reticulum stress and extracellular signal regulated 1/2-mediated apoptosis.