Intrinsic Mesenchymal Stem Cell Dysfunction in Diabetes Mellitus: Implications for Autologous Cell Therapy.

Mesenchymal stem cells derived from bone marrow (BM-MSCs) have multifunctional properties that have made them a promising therapeutic agent for many regenerative, anti-inflammatory, and autoimmune applications. Under chronic pathological conditions, however, BM-MSCs can become functionally compromised due to long-term exposure to changes in the systemic and localized stem cell niche microenvironments. In addition to the fact that functionally compromised BM-MSCs may be therapeutically ineffective, impairment of BM-MSCs is potentially a contributing factor to disease progression and development of comorbidities. For the purpose of this review, MSC-based therapies for treatment of nonhealing wounds in diabetic patients will be used as an example to demonstrate the effect that the diabetic host environment has on the regenerative capacity of endogenous BM-MSCs. This review will also discuss the mechanism by which the pathogenesis of diabetes mellitus leads to intrinsic dysfunction of the bone marrow stem cell niche that ultimately results in MSC failure and will highlight potential strategies for counteracting the functional decline of BM-MSCs.