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Teratoma formation leads to failure of treatment for type I diabetes using embryonic stem cell-derived insulin-producing cells.

Abstract
Embryonic stem (ES) cells have been proposed to be a powerful tool in the study of pancreatic disease, as well as a potential source for cell replacement therapy in the treatment of diabetes. However, data demonstrating the feasibility of using pancreatic islet-like cells differentiated from ES cells remain controversial. In this study we characterized ES cell-derived insulin-expressing cells and assessed their suitability for the treatment of type I diabetes. ES cell-derived insulin-stained cell clusters expressed insulin mRNA and transcription factors associated with pancreatic development. The majority of insulin-positive cells in the clusters also showed immunoreactivity for C-peptide. Insulin was stored in the cytoplasm and released into the culture medium in a glucose-dependent manner. When the cultured cells were transplanted into diabetic mice, they reversed the hyperglycemic state for approximately 3 weeks, but the rescue failed due to immature teratoma formation. Our studies demonstrate that reversal of hyperglycemia by transplantation of ES cell-derived insulin-producing cells is possible. However, the risk of teratoma formation would need to be eliminated before ES cell-based therapies for the treatment of diabetes are considered.
AuthorsTakahisa Fujikawa, Seh-Hoon Oh, Liya Pi, Heather M Hatch, Tom Shupe, Bryon E Petersen
JournalThe American journal of pathology (Am J Pathol) Vol. 166 Issue 6 Pg. 1781-91 (Jun 2005) ISSN: 0002-9440 [Print] United States
PMID15920163 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Insulin
  • RNA, Messenger
Topics
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Cell Differentiation (physiology)
  • Diabetes Mellitus, Type 1 (therapy)
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression
  • Immunohistochemistry
  • Insulin (biosynthesis)
  • Islets of Langerhans (cytology)
  • Mice
  • RNA, Messenger (analysis)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cell Transplantation (adverse effects)
  • Stem Cells (cytology, metabolism)
  • Teratoma (etiology)

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