Document Detail


Human marrow-derived mesodermal progenitor cells generate insulin-secreting islet-like clusters in vivo.
MedLine Citation:
PMID:  17999597     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transplantation of pancreatic islet cells is the only known potential cure for diabetes mellitus. However, the difficulty in obtaining sufficient numbers of purified islets for transplantation severely limits its use. A renewable and clinically accessible source of stem cells capable of differentiating into insulin-secreting beta-cells might circumvent this limitation. Here, we report that human fetal bone marrow (BM)-derived mesodermal progenitor cells (MPCs) possess the potential to generate insulinsecreting islet-like clusters (ISILCs) when injected into human fetal pancreatic tissues implanted in severe combined immunodeficiency (SCID) mice. Seven essential genes involved in pancreatic endocrine development, including insulin, glucagon, somatostatin, pdx-1, glut-2, nkx 2.2, and nkx 6.1, are expressed in these BM-MPC-derived ISILCs, suggesting that ISILCs are generated through neogenesis of BM-MPCs. Our data further suggest that differentiation of BM-MPCs into ISILCs is not mediated by cell fusion. Insulin secretion from these ISILCs is regulated by glucose concentration in vitro, and transplantation of purified ISILCs normalizes hyperglycemia in streptozocin (STZ)- induced nonobese diabetic (NOD)/SCID mice.
Authors:
Cuiwei Ai; Ivan Todorov; Marilyn L Slovak; David Digiusto; Stephen J Forman; Chu-Chih Shih
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells and development     Volume:  16     ISSN:  1547-3287     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-11-16     Completed Date:  2008-01-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  757-70     Citation Subset:  IM    
Affiliation:
Division of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010-3000, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD45 / metabolism
Bone Marrow Cells / cytology*
Cell Adhesion
Cell Fusion
Cell Proliferation
Cytogenetic Analysis
Fetus / cytology
Green Fluorescent Proteins / metabolism
Humans
Insulin / metabolism
Insulin-Secreting Cells / cytology*
Islets of Langerhans Transplantation
Mesoderm / cytology*
Mice
Mice, SCID
Phenotype
Stem Cells / cytology*
Grant Support
ID/Acronym/Agency:
CA 30206/CA/NCI NIH HHS; CA 33572/CA/NCI NIH HHS; CA 71866/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
11061-68-0/Insulin; 147336-22-9/Green Fluorescent Proteins; EC 3.1.3.48/Antigens, CD45

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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