MESENCHYMAL STEM CELL THERAPY FOR DIABETES

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall aim of this application is to use animal models to test the possibility that patients with diabetes can potentially be treated with the adult stem/progenitor cells from human bone marrow variously referred to as fibroblastoid colony forming units, mesenchymal stem cells, or multipotent mesenchymal stromal cells (MSCs). We and others previously demonstrated that MSCs have the remarkable property that they home to injured tissues and repair them. Recently, we found that after human MSCs were infused into immunodeficient mice with Type I diabetes, induced by streptozotocin (STZ)-injection; the human cells homed to the pancreas, activated ¿-cells, and increased secretion of mouse insulin sufficiently to lower blood glucose. The cells also homed to renal glomeruli and perhaps improved the pathological changes in the kidneys. The results therefore raised the possibility that administration of a large number of a patient's own MSCs may provide an effective means of repairing the damage to pancreatic and other tissues that occurs in diabetes. Our strategy is to examine the therapeutic potential of MSCs in a non-human primate model of Type I diabetes. The experiments will be central for our group to obtain data that can be used to develop an NIH grant application, as well as an Investigational New Drug (IND) application for a human clinical trial for patients with Type I diabetes. The Specific Aim for this proposal is to determine whether autologous MSCs, expanded ex vivo and reinfused into non-human primates with spontaneous Type I diabetes mellitus (T1DM) can improve ¿-cell function, lower blood glucose, improve glucose tolerance, and improve renal function. These experiments will extend the results of the mouse model studies to an animal species closely approximating the human form of T1DM. These experiments will extend the results of the mouse model studies to an animal species more closely related to humans, and have been designed to accelerate the translation to human clinical trials. The animals have been assigned to the project. Two rounds of bone marrow biopsies have been performed and MSCs isolated for future transplantation.