Human BM stem cells initiate angiogenesis in human islets in vitro

• Published in: Bone marrow transplantation (Basingstoke) Vol. 46; no. 8; pp. 1128 - 1137
• Main Authors: Luo, J Z Q, Xiong, F, Al-Homsi, A S, Roy, T, Luo, L G
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2011; Nature Publishing Group
• Subjects: 631/136/2060/16; 631/250/1620/1342; 692/698/1460/1583; 692/700/565/545/576/1955; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Angiogenesis; Angiogenic Proteins - metabolism; Angiogenin; Biological and medical sciences; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - physiology; Bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Biology; Cell Communication - physiology; Cell culture; Coculture Techniques; Endothelial cells; Gene expression; Genetic aspects; Glucagon; Hematology; Humans; Immunohistochemistry; Insulin; Internal Medicine; Islets of Langerhans; Islets of Langerhans - blood supply; Islets of Langerhans - cytology; Islets of Langerhans Transplantation - pathology; Islets of Langerhans Transplantation - physiology; Medical sciences; Medicine; Medicine & Public Health; Neovascularization; Neovascularization, Physiologic - physiology; Original; original-article; Physiological aspects; Platelet-derived growth factor; Public Health; Regeneration; Stem cell transplantation; Stem Cells; Stem Cells - cytology; Stem Cells - physiology; Tissue inhibitor of metalloproteinase 1; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Up-Regulation; Vascular endothelial growth factor; vascularization; United States; allogeneic BM; angiogenesis; human islet; Human; Angiogenesis; Hematology; Stem cell; Neovascularization; In vitro
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2010.278

BM stem cells may have regenerative effects on islet function through angiogenesis. Human islets (100 islet 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.