Editors' ChoiceDiabetes

The Skin(ny) on New β-Like Cells for Treating Diabetes

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Science Translational Medicine  21 Jul 2010:
Vol. 2, Issue 41, pp. 41ec114
DOI: 10.1126/scitranslmed.3001482

Diabetes affects approximately 3.5% of the population and invariably is associated with dysfunction of insulin-producing β cells in the pancreas. Although the disease can be treated with exogenous insulin, no pharmacological therapies to date target damaged β cells (the result of autoimmune destruction in type 1 diabetes) or insufficient β cell function (the result of insulin resistance in type 2 diabetes). Cell-based therapies designed to increase the ability of the pancreas to secrete endogenous insulin would revolutionize diabetes therapy and decrease dependence on exogenous insulin injections. However, current therapies focused on either whole pancreas/islet cell transplantation or autologous grafting of insulin-secreting cells from bone marrow– or liver-derived stem cells have been limited because of immune rejection or lack of primary tissue and restricted growth capacity, respectively.

Now, Alipio et al. demonstrate the feasibility of using induced pluripotent stem (iPS) cells derived from skin fibroblasts to generate β-like cells and reverse high blood sugar levels in mouse models of type 1 and type 2 diabetes. Specifically, a retroviral transduction system was used to “reprogram” normal mouse skin fibroblasts into iPS cells, and selective differentiation was then used to generate insulin-producing β-like cells. These cells were engrafted into the livers of the mice via intraportal vein injection. Not only did the engrafted cells produce insulin in response to glucose in vivo, but they led to normal blood glucose levels in the transplanted mice with type 1 diabetes and normal glycated hemoglobin levels—an indication of blood glucose concentration over time—in the transplanted mice with type 2 diabetes.

Collectively, these findings from two rodent models suggest that transplanted iPS cell–derived β-like cells may be able to restore endogenous in vivo insulin secretion and overcome the β cell dysfunction associated with type 1 and type 2 diabetes in humans—and thus have the potential to dramatically change how diabetes is treated.

Z. Alipio et al., Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic β-like cells. Proc. Natl. Acad. Sci. U.S.A. 7 July 2010 (10.1073/pnas.1007884107). [Full Text]

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