"The human umbilical cord is an increasingly popular source of cells being developed for cell therapy. The reasons, often reiterated, are the noninvasive harvest from tissue normally discarded at birth, the relatively high cell yields, and a phenotype that parallels that of mesenchymal stromal cells from other tissue sources. These cells are now being employed in human clinical trials, while also providing a cell source for an increasing number of preclinical and basic studies."
"Variations in allogeneic mesenchymal stem cell harvest levels from human tissues reflect the evolving nature of the field, patient demographic characteristics, and differences in harvest and isolation techniques. At present, Wharton’s jelly tissue yields the highest concentration of allogeneic mesenchymal stem cells whereas adipose tissue yields the highest levels of autologous mesenchymal stem cells per milliliter of tissue."
"Cells from the WJ offer the best clinical utility as (i) they have less non-stem cell contaminants (ii) can be generated in large numbers with minimal culture avoiding changes in phenotype, (iii) their derivation is quick and easy to standardize, (iv) they are rich in stemness characteristics and (v) have high differentiation potential."
"In species, such as humans, that evolved to regulate cell proliferation based on telomere length, high-turnover tissueswillbe affectedwith age.Telomere shortening in these tissues may be responsible for initiating whole body responses in a non-cell-autonomous way (Figure 1). Identifying these rate-limiting tissues will provide targets on which to direct telomerase therapiesthus correcting defects locally and possibly rescue whole body degeneration ."
"Multipotent stromal progenitor cells also known as Mesenchymal Stem Cells (MSCs) are pertinent tissue-specific stem cells in adult beings. The concept of MSC appears to be particularly interesting since this special type of precursor can bring forth a large spectrum of cell types as diverse as bone, cartilage, tendon, or fat precursor cells. MSCs are in the center of attention of many investigators due to easy isolation from many tissues. MSCs capability to differentiate into many cell types makes them a starting point of many new therapies, especially in tissue engineering."
"Mesenchymal stem cells (MSCs) are partially defined by their ability to differentiate into tissues including bone, cartilage and adipose in vitro, but it is their trophic, paracrine and immunomodulatory functions that may have the greatest therapeutic impact in vivo. Unlike pharmaceutical treatments that deliver a single agent at a specific dose, MSCs are site regulated and secrete bioactive factors and signals at variable concentrations in response to local microenvironmental cues. Significant progress has been made in understanding the biochemical and metabolic mechanisms and feedback associated with MSC response. The anti-inflammatory and immunomodulatory capacity of MSC may be paramount in the restoration of localized or systemic conditions for normal healing and tissue regeneration. "
"MSCs have been used therapeutically in clinical trials and subsequently in practice to treat graft-versus-host disease following bone marrow transplantation. Reports of successful immune modulation suggest efficacy in a wide range of autoimmune conditions, such as demyelinating neurological disease (multiple sclerosis), systemic lupus erythematosus, and Crohn’s disease, among others. This review provides background information about hMSCs and also describes their putative mechanisms of action in inflammation."
"The immune suppressive and anti-inflammatory properties of MSCs are now very well established and clearly encompass potent modulatory influences on the generation and disease-associated activity of multiple T-cell effector phenotypes [8-12]. Preclinical models provide a strong impetus for translating MSC therapy to widespread clinical use for a range of common, T-cellmediated autoimmune diseases and for prevention or treatment of transplant complications such as rejection and GvHD [8,10]."
"Osteoarthritis (OA) is the most common form of degenerative arthritis, mainly characterized by the degradation of articular cartilage and associated with subchondral bone lesions. Novel therapeutic approaches for OA include cell-based therapies that have become thriving areas of research and development. In this context, mesenchymal stem or stromal cells (MSCs) have gained much interest based on their trophic and immunomodulatory properties that can help tissue repair/regeneration. The present review article discusses the interest of using MSCs in cell-therapy approaches with a focus on the mechanisms by which MSCs might exhibit a therapeutic potential in OA. Special attention is given to the anti-inflammatory function of MSCs and on miRNA modulation in OA for possible future innovative strategies. The paper also presents the current data on the undergoing MSCs-based clinical trials in OA."
"Advancements during the last decade in the fields of regenerative medicine, tissue engineering, immunomodulatory therapy, and gene therapy have drawn us a step closer to making the application of stem cell therapy a feasible reality in the cure of T1D. However, a combinatorial approach that can combine safe and effective stem cell strategies with reliable existing therapies such as islet transplantation, as well as the latest immunosuppressive and immunomodulatory drug regimens and/or novel bioengineering techniques, would ensure an optimistic scenario for successful translation of stem cell therapy in the cure of T1D (Fig. 2). In short, the application of stem cell therapy in the cure for T1D appears extremely promising, with bona fide hope for a permanent cure."
"In the context of diabetes research, MSCs have been used to generate insulin-producing cells (10), counteract autoimmunity (11,12), enhance islet engraftment and survival (13,14), and to treat diabetic ulcers and limb ischemia (15). Also, MSC inoculum improved metabolic control in experimental models of type 2 diabetes (T2D) (16)."
"We confirmed a significant inhibition of hepatic regeneration when liver steatosis was present, while the hepatic regenerative response was promoted by infusion of MSCs. Specifically, MSC administration improved the hepatocyte proliferative response, PCNA-labeling index, DNA synthesis, liver function, and also reduced the number of apoptotic hepatocytes. These effects may be associated to the paracrine secretion of trophic factors by MSCs and the hepatic upregulation of key cytokines and growth factors relevant for cell proliferation, which ultimately improves the survival rate of the mice."
"Hair numbers were significantly increased after treatment in both male (including those without finasteride administration) and female patients. In the half-side comparison study, the increase in hair numbers was significantly higher on the treatment side than on the placebo side."
"Although several neurophysiological alterations have been associated with autism, immune abnormalities and neural hypoperfusion appear to be broadly consistent. These appear to be causative since correlation of altered inflammatory responses, and hypoperfusion with symptology is reported. Mesenchymal stem cells (MSC) are in late phases of clinical development for treatment of graft versus host disease and Crohn's Disease, two conditions of immune dysregulation. Cord blood CD34+ cells are known to be potent angiogenic stimulators, having demonstrated positive effects in not only peripheral ischemia, but also in models of cerebral ischemia. Additionally, anecdotal clinical cases have reported responses in autistic children receiving cord blood CD34+ cells. We propose the combined use of MSC and cord blood CD34+cells may be useful in the treatment of autism."
"A clinical trial of SC therapy for ED has been carried out in Korea . In this study, 7 T2DM men ranging from 57 to 87 years of age were each treated with IC injection of 15 million allogeneic umbilical cord blood SCs. Morning erection was regained in 3 patients within 1 month and in 6 patients within 3 months... Interestingly, SC therapy appears to have antidiabetes effects as all treated subjects except the oldest had reduced blood glucose and glycosylated hemoglobin levels. These results provide further evidence not only for the frequently observed antidiabetes effects of SCs but also for IC injection being a systemic application as we recently reported (see Stem cell transplantation section). Also noteworthy is that, despite being allogeneic in the absence of immunosuppressant, SC transplantation did not cause any adverse effects, thus providing further evidence for the immunosuppressive effects of SCs."