MESENCHYMAL STEM CELL THERAPY FOR DIABETES

间充质干细胞治疗糖尿病

• 批准号: 7716246
• 负责人: DARWIN Johnson PROCKOP
• 金额: $ 1.39万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716246
• 关键词: Adult; Animal Model; Animals; Applications Grants; Autologous; Blood Glucose; Bone Marrow; Bone marrow biopsy; Cell physiology; Cells; Clinical Trials; Colony-forming units; Computer Retrieval of Information on Scientific Projects Database; Data; Diabetes Mellitus; Funding; Future; Grant; Home environment; Human; Immunodeficient Mouse; Injection of therapeutic agent; Institution; Insulin; Insulin-Dependent Diabetes Mellitus; Investigational New Drug Application; Kidney; Kidney Glomerulus; Mesenchymal; Mesenchymal Stem Cells; Modeling; Mus; Numbers; Pancreas; Patients; Property; Renal function; Research; Research Personnel; Resources; Source; Stem cells; Streptozocin; Stromal Cells; Testing; Therapeutic; Tissues; Translations; Transplantation; United States National Institutes of Health; Wound Healing; design; glucose tolerance; improved; injured; mouse model; nonhuman primate; repaired; research study; stem; stem cell therapy

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 本申请的总体目标是使用动物模型来测试糖尿病患者是否有可能接受来自人骨髓的成体干细胞/祖细胞（分别称为成纤维细胞集落形成单位、间充质干细胞或多能间充质细胞）的治疗。我们和其他人之前证明，间充质干细胞具有可归巢并修复受损组织的显着特性，最近，我们发现将人类间充质干细胞注入免疫缺陷小鼠体内后。 I 型糖尿病，由链脲佐菌素 (STZ) 注射诱发；位于胰腺的人体细胞被激活 ¿细胞，并增加小鼠胰岛素的分泌，足以降低血糖，这些细胞也归巢于肾小球，并可能改善肾脏的病理变化。因此，结果提出了施用大量患者自身 MSC 的可能性。提供一种有效的方法来修复糖尿病引起的胰腺和其他组织的损伤。我们的策略是在非人类灵长类动物模型中检查间充质干细胞的治疗潜力，这些实验将是我们小组的核心。获取可用于开发 NIH 拨款申请以及针对 I 型糖尿病患者进行人体临床试验的研究性新药 (IND) 申请的数据。该提案的具体目标是确定自体 MSC 是否能够扩增。离体并回输至患有自发性 I 型糖尿病 (T1DM) 的非人类灵长类动物体内可以改善 ¿这些实验将小鼠模型研究的结果扩展到与人类 T1DM 密切相关的动物物种。 ，旨在加速向人体临床试验的转化，已对动物进行了两轮骨髓活检，并分离出 MSC 以供将来移植。