ABSTRACT
Human amniotic membrane-derived mesenchymal stem cells (hAM-MSCs) are capable of differentiating into several lineages and possess immunomodulatory properties. In this study, we investigated the soluble factor-mediated immunomodulatory effects of hAM-MSCs. Mitogen-induced peripheral blood mononuclear cell (PBMC) proliferation was suppressed by hAM-MSCs in a dose-dependent manner as well as hAM-MSC culture supernatant. Moreover, interferon-gamma and interleukin (IL)-17 production significantly decreased from PBMC, whereas IL-10 from PBMCs and transforming growth factor beta (TGF-beta) production from hAM-MSCs significantly increased in co-cultures of hAM-MSCs and PBMCs. Production of several MSC factors, including hepatocyte growth factor (HGF), TGF-beta, prostaglandin E2 (PGE2), and indoleamine 2, 3 dioxygenase (IDO), increased significantly in hAM-MSCs co-cultured with PBMCs. These results indicate that the immunomodulatory effects of hAM-MSCs may be associated with soluble factors (TGF-beta, HGF, PGE2, and IDO), suggesting that hAM-MSCs may have potential clinical use in regenerative medicine.
Subject(s)
Female , Humans , Pregnancy , Amnion/cytology , Cell Differentiation/immunology , Coculture Techniques , Dinoprostone/genetics , Hepatocyte Growth Factor/genetics , Immunologic Factors/immunology , Immunophenotyping , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Interferon-gamma/immunology , Interleukin-10/analysis , Interleukin-17/analysis , Leukocytes, Mononuclear/cytology , Mesenchymal Stem Cells/cytology , RNA, Messenger/chemistry , Regenerative Medicine/methods , Reverse Transcriptase Polymerase Chain Reaction , Transforming Growth Factor beta/geneticsABSTRACT
Islet transplantation has the potential to restore normoglycemia and prevent the development of diabetic complications such as retinopathy, nephropathy and neuropathy, and could therefore ve a valuable treatment for diabetic patients. The scarcity of available islets is an obstacle for clinically successful islet transplantation. To resolve the problems, we have examined the two methods, islet transplantation with extracellular matrix1 and in vivo expansion of islets with electrically- transfection of growth factors.
Subject(s)
Animals , Male , Rats , Diabetes Mellitus/surgery , Fibronectins/therapeutic use , Hepatocyte Growth Factor/genetics , Islets of Langerhans/drug effects , Islets of Langerhans Transplantation , Rats, Wistar , Regeneration , TransfectionABSTRACT
Hepatocyte growth factor (HGF) is a potent mitogen and promoter of proliferation of insulin producing beta cells of pancreatic islets. To study the role of HGF, an adenoviral vector carrying the human HGF (Ad.hHGF) gene was transfected into the streptozotocin-induced diabetic mice and evaluated the effect on the blood glucose metabolism and the insulin-secreting beta cells of pancreatic islets. Ad.hHGF gene transfection resulted in amelioration of hyperglycemia and prolongation of survival period in the diabetic mice. Concomitantly adenoviral- mediated hHGF gene therapy slightly increased serum insulin concentration and the expression of insulin in the pancreatic islet. Although the proliferation of beta-cell mass was not noticeable, the beneficial effect of HGF is significant to an almost deteriorated pancreatic islets. Taken together, these data suggest that the Ad.hHGF gene therapy into diabetic mice may prevent the further destruction and present as a beneficial remedy for type 1 diabetic patients.