Mccall M.D.,University of Alberta |
Toso C.,University of Alberta |
Baetge E.E.,Novocell Inc. |
Shapiro A.M.J.,University of Alberta
Clinical Science | Year: 2010
With the already heightened demand placed on organ donation, stem cell therapy has become a tantalizing idea to provide glucose-responsive insulin-producing cells to Type 1 diabetic patients as an alternative to islet transplantation. Multiple groups have developed varied approaches to create a population of cells with the appropriate characteristics. Both adult and embryonic stem cells have received an enormous amount of attention as possible sources of insulin-producing cells. Although adult stem cells lack the pluripotent nature of their embryonic counterparts, they appear to avoid the ethical debate that has centred around the latter. This may limit the eventual application of embryonic stem cells, which have already shown promise in early mouse models. One must also consider the potential of stem cells to form teratomas, a complication which would prove devastating in an immunologically compromised transplant recipient. The present review looks at the progress to date in both the adult and embryonic stem cells fields as potential treatments for diabetes. We also consider some of the limitations of stem cell therapy and the potential complications that may develop with their use. © The Authors Journal compilation © 2010 Biochemical Society.
Wang Y.,University of Houston |
Klumpp S.,University of Houston |
Amin H.M.,University of Houston |
Liang H.,University of Houston |
And 6 more authors.
Oncogene | Year: 2010
SSBP proteins bind and stabilize transcriptional cofactor LIM domain-binding protein1 (LDB1) from proteosomal degradation to promote tissue-specific transcription through an evolutionarily conserved pathway. The human SSBP2 gene was isolated as a candidate tumor suppressor from a critical region of loss in chromosome 5q14.1. By gene targeting, we show increased predisposition to B-cell lymphomas and carcinomas in Ssbp2/mice. Remarkably, loss of Ssbp2 causes increased LDB1 turnover in the thymus, a pathway exploited in Trp53/Ssbp2/mice to develop highly aggressive, immature thymic lymphomas. Using T-cell differentiation as a model, we report a stage-specific upregulation of Ssbp2 expression, which in turn regulates LDB1 turnover under physiological conditions. Furthermore, transcript levels of pTα, a target of LDB1-containing complex, and a critical regulator T-cell differentiation are reduced in Ssbp2/immature thymocytes. Our findings suggest that disruption of the SSBP2-regulated pathways may be an infrequent but critical step in malignant transformation of multiple tissues. © 2010 Macmillan Publishers Limited All rights reserved.
ViaCyte, Inc. and Novocell Inc. | Date: 2011-04-26
ViaCyte, Inc. and Novocell Inc. | Date: 2009-10-28
Kelly O.G.,ViaCyte, Inc. |
Kelly O.G.,Novocell Inc. |
Chan M.Y.,ViaCyte, Inc. |
Chan M.Y.,Novocell Inc. |
And 22 more authors.
Nature Biotechnology | Year: 2011
Using a flow cytometry-based screen of commercial antibodies, we have identified cell-surface markers for the separation of pancreatic cell types derived from human embryonic stem (hES) cells. We show enrichment of pancreatic endoderm cells using CD142 and of endocrine cells using CD200 and CD318. After transplantation into mice, enriched pancreatic endoderm cells give rise to all the pancreatic lineages, including functional insulin-producing cells, demonstrating that they are pancreatic progenitors. In contrast, implanted, enriched polyhormonal endocrine cells principally give rise to glucagon cells. These antibodies will aid investigations that use pancreatic cells generated from pluripotent stem cells to study diabetes and pancreas biology. © 2011 Nature America, Inc. All rights reserved.