TRANSPLANTATION OF MULTIPOTENT PROGENITOR CELLS IN STROKE

中风患者多能祖细胞的移植

• 批准号: 7666913
• 负责人: CESARIO V BORLONGAN
• 金额: --
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7666913
• 关键词: TRANSPLANTATION; MULTIPOTENT; PROGENITOR; CELLS; STROKE

DESCRIPTION (provided by applicant): Multipotent progenitor cells (MFCs) (Nature, 418:41-49, 2002), developed by Dr. Verfaillie and co- workers at the University of Minnesota, appear to have the properties which make them highly suitable as a stem cell therapy. Athersys, Inc. has the proprietary rights to these cells. We have recently developed a collaborative relationship with Athersys, Inc. which has developed manufacturing techniques to make these cells available for clinical use. Athersys, Inc. will supply these cells to us. Our preliminary data in rodents indicate that these cells are quite promising as a therapy for stroke. In order to develop the utility of these cells in stroke, we propose a translational protocol. The proposed set of experiments will serve as the preclinical basis for proceeding with transplantation of MFCs in ischemic stroke patients. Feasibility, safety, and optimal MFC dose and transplantation timing post- stroke for producing efficacy in rodent models of adult ischemic stroke will be examined. The following specific aims will serve as milestones, with "go and no-go" criteria. Specific Aim 1: Determine the "long-term" (i.e., 6 months post-transplantation) efficacy of IV rat MPCs in transient middle cerebral artery occlusion model. Specific Aim 2: Evaluate the long-term efficacy of IV human MPCs produced by Athersys, Inc. according to GMP manufacturing protocols in a GLP xenogeneic transient middle cerebral artery occlusion model. Specific Aim 3: Assess the efficacy of IV human MPCs to achieve long-term behavioral benefits in male and female, and adult and aged rats exposed to transient middle cerebral artery occlusion model. Specific Aim 4: Demonstrate the efficacy of IV human MPCs to achieve long-term behavioral benefits in permanent middle cerebral artery ligation model. Specific Aim 5: Characterize stem cell histocompatibility in allogeneic rat MPCs and xenogeneic human MPCs to further provide safety of IV MPCs in rat ischemic stroke model. Specific Aim 6: Conduct IND FDA preparation meetings and assemble documents for filing IND for stem cell therapy in ischemic stroke. This proposal extends our scientific platform for determining the benefit of stem cell therapy in stroke.

描述（由申请人提供）： 由Verfaillie博士和明尼苏达大学的同事开发的多晶祖细胞（MFCS）（自然，418：41-49，2002）似乎具有使它们非常适合作为干细胞疗法的特性。 Athersys，Inc。拥有这些细胞的专有权利。我们最近与Athersys，Inc。建立了合作关系，该公司开发了制造技术以使这些细胞可用于临床使用。 Athersys，Inc。将向我们提供这些细胞。我们在啮齿动物中的初步数据表明，这些细胞作为中风的疗法非常有前途。为了在中风中开发这些细胞的效用，我们提出了一种翻译方案。拟议的一组实验将作为进行缺血性中风患者移植MFC的临床前基础。将检查可行性，安全性和最佳的MFC剂量和移植时间，以在成年缺血性中风的啮齿动物模型中产生功效。以下特定目标将作为里程碑，并具有“ GO和No-Go”标准。具体目标1：确定IV大鼠MPC在短暂性中大脑动脉闭塞模型中的“长期”（即移植后6个月）的功效。具体目标2：评估Athersys，Inc。在GMP制造方案中，在GMP制造方案中评估IV人类MPC的长期疗效。特定目的3：评估IV人MPC在男性和女性中实现长期行为益处的功效，以及暴露于短暂性中大脑动脉闭塞模型的成年大鼠。特定目的4：证明IV人MPC在永久性大脑中动脉连接模型中实现长期行为益处的功效。具体目标5：表征同种异体大鼠MPC和异类人MPC中干细胞组织相容性，以进一步提供IV MPC在大鼠缺血性中风模型中的安全性。具体目的6：进行IND FDA准备会议和组装文件，以归档缺血性中风中的干细胞治疗。该提案扩展了我们的科学平台，以确定干细胞疗法在中风中的好处。