Mesenchymal Stem Cell-Based Treatment for Microvascular and Secondary Complications of Diabetes Mellitus

Abstract

The worldwide increase in the prevalence of Diabetes mellitus (DM) has highlighted the need for increased research efforts into treatment options for both the disease itself and its associated complications. In recent years, mesenchymal stromal cells (MSCs) have been highlighted as a new emerging regenerative therapy due to their multipotency but also due to their paracrine secretion of angiogenic factors, cytokines, and immunomodulatory substances. This review focuses on the potential use of MSCs as a regenerative medicine in microvascular and secondary complications of DM and will discuss the challenges and future prospects of MSCs as a regenerative therapy in this field. MSCs are believed to have an important role in tissue repair. Evidence in recent years has demonstrated that MSCs have potent immunomodulatory functions resulting in active suppression of various components of the host immune response. MSCs may also have glucose lowering properties providing another attractive and unique feature of this therapeutic approach. Through a combination of the above characteristics, MSCs have been shown to exert beneficial effects in pre-clinical models of diabetic complications prompting initial clinical studies in diabetic wound healing and nephropathy. Challenges that remain in the clinical translation of MSC therapy include issues of MSC heterogeneity, optimal mode of cell delivery, homing of these cells to tissues of interest with high efficiency, clinically meaningful engraftment, and challenges with cell manufacture. An issue of added importance is whether an autologous or allogeneic approach will be used. In summary, MSC administration has significant potential in the treatment of diabetic microvascular and secondary complications but challenges remain in terms of engraftment, persistence, tissue targeting, and cell manufacture

Progenitor Cell Dysfunctions Underlie Some Diabetic Complications

“…104 Similarly, bone marroweMSC and ASC transplants have been tested for the modulation of diabetic nephropathy and for the treatment of nonhealing diabetic wounds resulting from neuropathy and microvasculopathy. 14,105,106 This section details the various approaches of using autologous stem cells for treating diabetic complications.…”

Bone Marrow-Derived Mesenchymal Stem cells Infusion Ameliorates Hyperglycemia, Dyslipidemia, Liver and Kidney Functions in Diabetic Rats

“…Diabetic nephropathy (DN), one of the most serious micro vascular complications of diabetes, is a major cause of end stage renal disease that is reflected by proteinuria, decreased creatinine clearance, elevated urea, uric acid and creatinine levels [64], [65]. In the present study the STZ induced diabetic rats developed symptoms of renal dysfunction, as shown by elevated serum urea, uric acid and creatinine concentrations.…”

Use of Human Embryonic Stem Cells in the Treatment of Diabetes Mellitus: A Case Series

“…Stem cells that have been investigated in the treatment of DM include pluripotent stem cells (PSCs), mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs) [7] [21] [22].…”