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Presenter: J., Gold, Chicago, USA
Authors: J. Gold, K. Lu, J. Jiang, M. Au, L. Zhao, C. Priest, P. Moore, C. Rhodes
Human embryonic stem cell-derived therapy for diabetes: in vitro and in vivo assessments reveal distinct characteristics
J. Gold1, K. Lu1, J. Jiang1, M. Au1, L. Zhao1, C. Priest1, P. Moore2, C. Rhodes2
1 Geron Corporation, Menlo Park, USA; 2 U. Chicago, Chicago, USA
Objective: To assess potential human embryonic stem-derived therapies for diabetes for both in vitro characteristics and in vivo function.
Methods: A unique protocol designed to induce pancreatic cell differentiation from hESC line H1 was used to generate definitive endoderm, pancreatic progenitors, and islet hormone-producing cells. The resultant cells were characterized by flow cytometry, ICC, quantitative PCR and HPLC methods. Cells at different stages were transplanted into rodents and examined for their ability to produce glucose-responsive human insulin and protect the animals from STZ-induced diabetes. Resultant grafts were assessed histologically.
Results: Cultures containing 20-25% c-peptide+ were generated; these cells secreted human insulin in response to glucose challenge. However, these cells had a phenotype distinct from mature beta cells: single cells expressed multiple islet hormones and some transcription factors associated with mature beta cells were not expressed. Transplantation of cells at an earlier stage of differentiation proved more efficient at in vivo function and protection against STZ-induced diabetes; histological examination of the resultant grafts demonstrated the presence of islet cells with mature phenotypes.
Conclusions: Endocrine progenitor cells, rather than hormone-expressing cells may be better candidates for diabetes cell therapies- these cells mature in vivo to form grafts that are effective at maintaining glucose homeostasis in STZ-treated mice. In addition, although in vitro differentiation may produce cells with some of the hallmarks of beta cells, careful characterization of the resultant cells is warranted.
Disclosure: Employee of and stockholder in Geron Corporation
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