Maehr, R. et al. Generation of pluripotent stem cells from patients with type 1 diabetes. Proc. Natl Acad. Sci. USA 106, 15768-15773

Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 09/2009; 106(37):15768-73. DOI: 10.1073/pnas.0906894106
Source: PubMed


Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic beta cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would be useful for disease modeling. We show here that induced pluripotent stem (iPS) cells can be generated from patients with T1D by reprogramming their adult fibroblasts with three transcription factors (OCT4, SOX2, KLF4). T1D-specific iPS cells, termed DiPS cells, have the hallmarks of pluripotency and can be differentiated into insulin-producing cells. These results are a step toward using DiPS cells in T1D disease modeling, as well as for cell replacement therapy.

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Available from: René Maehr, Nov 17, 2014
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    • "Human induced pluripotent stem cells (iPSCs) technology had been successfully generated via the retrovirus-mediated transfection of four transcription factors (Oct4, Sox2, Klf-4, and c-Myc) (Takahashi et al., 2007; Yu et al., 2007). Several studies had been made to generate iPSCs from patients with various diseases providing new opportunities for regenerative medicine and in vitro disease modeling (Dimos et al., 2008; Park et al., 2008; Maehr et al., 2009). Among disease, those involving retina are necessary and urgent to consider for iPSCs modeling, because of these tissue are not amenable to routine biopsy. "
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    • "At present, it is of special interest for the diabetes community to find a way to produce ex vivo pancreatic cell masses to restore biological functions that are lost due to cellular deficits. Because T1D only affects a single cell type, T1D can be treated with novel cellular replacement therapies that are based on reprogramming human embryonic stem cells (hESC) [2] or with human induced pluripotent stem cells (hiPSC) [3], [4] into pancreatic-like cells. However, hESC and hiPSC show several disadvantages, such as ethical problems [5], transgenic strategies [6] or epigenetic failure [7], which limit their use to in vitro assays or preclinical models [8]. "
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    ABSTRACT: The conversion of differentiated cells into insulin-producing cells is a promising approach for the autologous replacement of pancreatic cells in patients with type 1 diabetes (T1D). At present, cellular reprogramming strategies encompass ethical problems, epigenetic failure or teratoma formation, which has prompted the development of new approaches. Here, we report a novel technique for the conversion of skin fibroblasts from T1D patients into insulin-expressing clusters using only drug-based induction. Our results demonstrate that skin fibroblasts from diabetic patients have pancreatic differentiation capacities and avoid the necessity of using transgenic strategies, stem cell sources or global demethylation steps. These findings open new possibilities for studying diabetes mechanisms, drug screenings and ultimately autologous transgenic-free regenerative medicine therapies in patients with T1D.
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    • "Activin A has been used to induce DE cells in most reports. More recently, it has been shown that the combination of activin A with Wnt3a results in more efficient induction of DE cells11141618212526. In addition to these factors, we chose six growth factors and small molecules from other relevant reports, and examined the differentiation efficiency of DE cells by changing the combinations and concentrations of these factors (Table S1). "
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