Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) are a prototypic adult stem cell with capacity for self-renewal and differentiation with a broad tissue distribution. Initially described in bone marrow, MSCs have the capacity to differentiate into mesodermal and non-mesodermal derived tissues. The endogenous role for MSCs is maintenance of stem cell niches (classically the hematopoietic), and as such MSCs participate in organ homeostasis, wound healing, and successful aging. From a therapeutic perspective, and facilitated by the ease of preparation and immunologic privilege, MSCs are emerging as an extremely promising therapeutic agent for tissue regeneration. Studies in animal models of myocardial infarction (MI) demonstrate the ability of transplanted MSCs to engraft and differentiate into cardiomyocytes and vasculature cells, recruit endogenous cardiac stem cells, and secrete a wide array of paracrine factors. Together these properties can be harnessed to both prevent and reverse remodeling in the ischemically injured ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improve LV function, induces reverse remodeling, and decreases scar size. This article reviews the current understanding of MSC biology, mechanism of action in cardiac repair, translational findings, and early clinical trial data of MSC therapy for cardiac disease.

Allogeneic Mesenchymal Stromal Cells Transplanted Onto the Heart Surface Achieve Therapeutic Myocardial Repair Despite Immunologic Responses in Rats

“…Flow cytometric study and differentiation assay demonstrated that CD marker expression (Figure 1A), adipogenic and osteogenic differentiation (Figure 1B and 1C), and MHC class I and II expression (Figure 1D) were all compatible for the 2 types of MSCs. In addition, quantitative polymerase chain reaction showed that expression of reparative factors ( VEGF, IGF1, SDF1, and HIF1A ), which are proposed to play a role in MSC‐mediated myocardial repair,1, 11 was not statistically different between Lewis‐ and Fischer 344–derived MSCs (n=4 per group, Wilcoxon rank sum test) (data not shown).…”

“…Recent preclinical and clinical research has suggested that transplantation of bone marrow–derived mesenchymal stromal cells (MSCs) is a promising new approach for the treatment of heart failure 1. Although cardiomyogenic differentiation of these cells in vivo is limited, MSCs are able to induce therapeutic benefits by secreting various biological factors that promote repair of the failing myocardium (ie, paracrine effects).…”

“…Moreover, MSCs from older patients with comorbidities might undermine therapeutic competencies and reduce the ability to expand in vitro 2. In response to these issues, the use of allogeneic MSCs has been proposed on account of their immune‐modulating ability and their relatively low immunogenic phenotype 1, 3. Previous reports have shown that injection of allogeneic MSCs, without immunosuppressive treatment, improved cardiac function to the same extent as autologous (syngeneic) MSCs in experimental myocardial infarction (MI) models 4, 5, 6.…”

Mesenchymal stem cell‐loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium

“…There are several candidate stem cells for cardiac transplantation that have been recently evaluated 5, 6. Compared with cardiac progenitor cells, embryonic or induced pluripotent stem cells, mesenchymal stem cells (MSCs) have been considered a very promising cell population for cardiac transplantation because it is easily isolated from bone marrow or adipose tissue and exhibits low immunogenicity and cardiomyocyte, vascular smooth muscle and endothelial cell differentiation potential, although this cardiogenic potential remains controversial 7, 8. Cardiac cell therapy ( via intracoronary or intracardial injection) is limited by poor engraftment and significant cell death after transplantation 9, 10.…”

Glyoxalase-1 Overexpression Reverses Defective Proangiogenic Function of Diabetic Adipose-Derived Stem Cells in Streptozotocin-Induced Diabetic Mice Model of Critical Limb Ischemia

“…The recent application of stem cell therapy in the clinical management of ischemic diseases has shown encouraging results by increasing neovascularization and blood flow in the ischemic tissue to induce wound perfusion and healing 5 6 7. Because T2DM is often accompanied by obesity, these patients possess a huge reservoir of adipose‐derived stem cells (ADSCs) for stem cell therapy.…”