Influence of Human Allogenic Bone Marrow and Cord Blood–Derived Mesenchymal Stem Cell Secreting Trophic Factors on ATP (adenosine-5′-triphosphate)/ADP (adenosine-5′-diphosphate) Ratio and Insulin Secretory Function of Isolated Human Islets From Cadaveric Donor

• Published in: Transplantation proceedings 2009-11, Vol.41 (9), p.3813-3818
• Main Authors: Park, K.S, Kim, Y.S, Kim, J.H, Choi, B.K, Kim, S.H, Oh, S.H, Ahn, Y.R, Lee, M.S, Lee, M.K, Park, J.B, Kwon, C.H, Joh, J.W, Kim, K.W, Kim, S.J
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Triphosphate - metabolism; Biological and medical sciences; Bone Marrow Cells - cytology; Cadaver; Cell Separation - methods; Centrifugation, Density Gradient; Coculture Techniques; Cord Blood Stem Cell Transplantation - methods; Diabetes Mellitus, Type 1 - surgery; Enzyme-Linked Immunosorbent Assay; Fetal Blood - cytology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Islets of Langerhans - cytology; Islets of Langerhans Transplantation - methods; Medical sciences; Mesenchymal Stromal Cells - cytology; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue Donors; Tissue, organ and graft immunology
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2009.06.193

Abstract Successful islet transplantation (ITx) is not only dependent on the number of islets, but also their quality, including viability, metabolic activity, and function. Islet quality decreases during cultivation after the isolation procedure. To overcome this obstacle, we established the practice of islet and mesenchymal stem cells (MSCs) coculture. This coculture condition improved the ATP (adenosine-5′-triphosphate)/ADP (adenosine-5′-diphosphate) ratio and insulin secretory function in vitro. It is believed that the enhancement of islet quality in islet-MSCs cocultures may be caused by the secretion of active agents by MSCs. Herein we have shown that interleukin-6 (IL-6), vascular endothelial growth factor-A (VEGF-A), hepatocyte growth factor (HGF), and transforming growth factor-β (TGF-β) were significantly increased as measured by enzyme-linked immunosorbent assay (ELISA) in MSCs-cultured medium, factors that have been shown to improve the survival, function, and angiogenesis/revascularization of islets. These results indicated that the quality of human islets was enhanced by trophic molecules secreted by MSCs, which influence the intracellular islet ATP content and insulin secretory function.