William Shank

Introduction. Type I diabetes mellitus (T1D) is a chronic disease characterized by autoimmune destruction of pancreatic β-cells leading to chronic insufficient insulin production. Lymphocytic infiltration and destruction of these cells, along with circulating islet cell antibodies and anti-insulin antibodies are seen in T1D patients^1,2. Treatment of T1D currently requires lifelong exogenous insulin therapy to maintain normal blood glucose levels². However, T1D continues to be associated with high morbidity and premature mortality^1,2. Development of treatments for T1D has undergone a recent paradigm shift aimed at prevention of disease progression by maintaining endogenous beta cell function. Human mesenchymal stem cells (MSCs) are non-hematopoietic, multipotent cells that can be isolated from several tissue types, cultured long-term without any severe abnormalities, and are capable of secreting cytokines and chemokines that can regulate their nearby environment^3,4. These features have made them a popular area of study for their use in treatment of chronic disease, including T1D⁴. Studies have been done on both non-obese diabetic (NOD) mouse models and in human subjects using MSCs as a therapy for T1D. Methods. In this review, several studies conducted on both NOD mice and in human subjects have been examined to present and discuss the ameliorating effects of MSC therapy in autoimmune diabetes and the possible mechanism of these effects. Results. 78% of NOD mice, with early-onset diabetes, showed reversal of hyperglycemia with intraperitoneal injections of adipose-derived MSCs. The treated mice also showed reduced inflammation of pancreatic islet cells and higher expression of insulin compared the untreated NOD mice group⁵. NOD mice with simultaneous transplantation of pancreatic islet cells and MSCs showed decreased blood glucose and increased number of pancreatic islet cells when compared to controls⁶. 20 adult patients with new-onset diabetes showed increased C-peptide levels a year after MSC therapy⁷. Autologous MSC therapy from newly diagnosed T1D patients showed similar beneficial effects when compared to MSCs from healthy patients⁸. MSC-treated NOD mice showed increased levels of transcription factors pAkt and pErk when compared to controls, suggesting they may play a role in beta cell proliferation in the context of MSC therapy for T1D⁹. Conclusions. The multiple encouraging results of MSC therapy for T1D in both mice and humans suggest the need for further research into the underlying mechanism of action of MSC therapy. Ultimately, future studies should investigate the efficacy of MSC therapy compared to traditional insulin therapy.

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