Human BM stem cells initiate angiogenesis in human islets in vitro.
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.
Roger Williams Medical Center, Boston University, Providence, RI 02908, USA. Lluo@rwmc.org
J Z Q
JZ
Luo
F
F
Xiong
A S
AS
Al-Homsi
T
T
Roy
L G
LG
Luo
D042501:Angiogenic Proteins / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D018920:Coculture Techniques; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000098:blood supply* / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000473:pathology / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D015854:Up-Regulation
D042501:Angiogenic Proteins