Journal Article

Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic β-like cells

Waner, Milton, Ward, David C, Fink, Louis M, Roemer, Elizabeth J, Ma, Yupo, Alipio, Zaida, Liao, Wenbin

2010

Overview

Diabetes mellitus is characterized by either the inability to produce insulin (type 1 diabetes) or as insensitivity to insulin secreted by the body (type 2 diabetes). In either case, the body is unable to move blood glucose efficiently across cell membranes to be used. This leads to a variety of local and systemic detrimental effects. Current treatments for diabetes focus on exogenous insulin administration and dietary control. Here, we describe a potential cure for diabetes using a cellular therapy to ameliorate symptoms associated with both reduced insulin secretion and insulin sensitivity. Using induced pluripotent stem (iPS) cells, we were able to derive β-like cells similar to the endogenous insulin-secreting cells in mice. These β-like cells secreted insulin in response to glucose and corrected a hyperglycemic phenotype in two mouse models of type 1 and 2 diabetes via an iPS cell transplant. Long-term correction of hyperglycemia was achieved, as determined by blood glucose and hemoglobin A1c levels. These data provide an initial proof of principle for potential clinical applications of reprogrammed somatic cells in the treatment of diabetes type 1 or 2.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: animal disease models / Animals / Beta cells / Biological Sciences / blood glucose / Blood Glucose - analysis / Cell Differentiation / cell membranes / Cell Transplantation - methods / Cells, Cultured / Cellular differentiation / Diabetes complications / Diabetes Mellitus, Type 1 - complications / Diabetes Mellitus, Type 1 - surgery / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - surgery / Disease Models, Animal / Fluorescent Antibody Technique / glucose / Glycated Hemoglobin A - analysis / glycohemoglobin / Green Fluorescent Proteins - genetics / Green Fluorescent Proteins - metabolism / Humans / Hyperglycemia / Hyperglycemia - blood / Hyperglycemia - complications / Hyperglycemia - prevention & control / Induced pluripotent stem cells / Induced Pluripotent Stem Cells - cytology / Induced Pluripotent Stem Cells - metabolism / Induced Pluripotent Stem Cells - transplantation / Insulin / Insulin - analysis / Insulin - metabolism / insulin resistance / Insulin Secretion / insulin-dependent diabetes mellitus / Insulin-Secreting Cells - cytology / Insulin-Secreting Cells - metabolism / Insulin-Secreting Cells - transplantation / Mice / Mice, Inbred C57BL / Mice, Inbred DBA / Mice, Nude / Mice, Transgenic / noninsulin-dependent diabetes mellitus / phenotype / Somatic cells / therapeutics / Transplantation / Type 1 diabetes mellitus / Type 2 diabetes mellitus