Stem cells in the treatment of diabetes mellitus — Focus on mesenchymal stem cells

Diabetes mellitus type 1 and type 2 have become a global epidemic with dramatically increasing incidences. Poorly controlled diabetes is associated with severe life-threatening complications. Beside traditional treatment with insulin and oral anti-diabetic drugs, clinicians try to improve patient's care by cell therapies using embryonic stem cells (ESC), induced pluripotent stem cells (iPSC) and adult mesenchymal stem cells (MSC). ESC display a virtually unlimited plasticity, including the differentiation into insulin producing β-cells, but they raise ethical concerns and bear, like iPSC, the risk of tumours. IPSC may further inherit somatic mutations and remaining somatic transcriptional memory upon incomplete re-programming, but allow the generation of patient/disease-specific cell lines. MSC avoid such issues but have not been successfully differentiated into β-cells. Instead, MSC and their pericyte phenotypes outside the bone marrow have been recognized to secrete numerous immunomodulatory and tissue regenerative factors. On this account, the term ‘medicinal signaling cells’ has been proposed to define the new conception of a ‘drug store’ for injured tissues and to stay with the MSC nomenclature. This review presents the biological background and the resulting clinical potential and limitations of ESC, iPSC and MSC, and summarizes the current status quo of cell therapeutic concepts and trials. •Large-scale production of pancreatic endoderm and β-cells from embryonic stem cells•First-in-man trial investigates macroencapsulated embryonic stem cell-derived β-cells•Induced pluripotent stem cells allow patient/disease-specific cell lines•Mesenchymal stem cells secrete immunomodulatory and tissue regenerative factors•Transplanted mesenchymal stem cells ameliorate human type 1 and type 2 diabetes