Human BM stem cells initiate angiogenesis in human islets in vitro

Bone Marrow Transplant. 2011 Aug;46(8):1128-37. doi: 10.1038/bmt.2010.278. Epub 2010 Dec 6.

Abstract

BM stem cells may have regenerative effects on islet function through angiogenesis. Human islets (100islet equivalent/mL) were cultured alone (control) or co-cultured (experimental group) with whole human BM (1 × 10(6) cells/mL) for 210 days. A protein array measuring angiogenesis factors found upregulated (experimental vs control, day 210) proteins levels of VEGF-a (535 vs 2 pg/mL), PDGF (280.79 vs 0 pg/mL), KGF (939 vs 8 pg/mL), TIMP-1 (4592 vs 4332 pg/mL) and angiogenin (506 vs 97 pg/mL). Lower protein levels of angiopoietin-2 (5 vs 709 pg/mL) were observed. Depletion of pro-angiogenesis factors in co-culture decreased the effects of BM-induced islet vascularization. Depletion of VEGF-a, eKGF and PDGF significantly reduced islet vascularization but individual depletion of KGF and PDGF had less effects overall on vessel formation. BM-induced vascularization showed significant endothelial cell distribution. Islet vascularization was linked to islet growth. A decrease in islet size indicated poor vascularization. Insulin release was evident in the tissues generated from human islet-BM co-culture throughout the entire culture period. Significant increase in insulin (28.66-fold vs control) and glucagon (24.4-fold vs control) gene expression suggest BM can induce endocrine cell regeneration. In conclusion, BM promotes human islet tissue regeneration via regulation of angiogenesis factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenic Proteins / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology*
  • Cell Communication / physiology
  • Coculture Techniques
  • Humans
  • Immunohistochemistry
  • Islets of Langerhans / blood supply*
  • Islets of Langerhans / cytology
  • Islets of Langerhans Transplantation / pathology
  • Islets of Langerhans Transplantation / physiology*
  • Neovascularization, Physiologic / physiology
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Up-Regulation

Substances

  • Angiogenic Proteins