TRANSPLANTATION OF MULTIPOTENT PROGENITOR CELLS IN STROKE

中风患者多能祖细胞的移植

• 批准号: 7382844
• 负责人: CESARIO V BORLONGAN
• 金额: $ 21.28万
• 依托单位: AUGUSTA UNIVERSITY
• 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 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382844
• 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）： 明尼苏达大学的 Verfaillie 博士及其同事开发的多能祖细胞 (MFC)（Nature，418:41-49, 2002）似乎具有使其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，使这些细胞可供临床使用。 Athersys, Inc. 将向我们提供这些细胞。我们在啮齿动物身上的初步数据表明，这些细胞非常有希望作为中风的治疗方法。为了开发这些细胞在中风中的效用，我们提出了一种转化方案。拟议的一组实验将作为在缺血性中风患者中进行 MFC 移植的临床前基础。将检查可行性、安全性以及最佳 MFC 剂量和中风后移植时机，以在成人缺血性中风的啮齿动物模型中产生功效。以下具体目标将作为里程碑，并具有“可行和不可行”的标准。具体目标 1：确定 IV 大鼠 MPC 在短暂大脑中动脉闭塞模型中的“长期”（即移植后 6 个月）功效。具体目标 2：评估 Athersys, Inc. 根据 GMP 制造协议在 GLP 异种暂时性大脑中动脉闭塞模型中生产的 IV 人 MPC 的长期疗效。具体目标 3：评估静脉注射人类 MPC 在暴露于短暂大脑中动脉闭塞模型的雄性和雌性、成年和老年大鼠中实现长期行为益处的功效。具体目标 4：证明 IV 人类 MPC 在永久性大脑中动脉结扎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 和异种人类 MPC 中的干细胞组织相容性，以进一步提供 IV MPC 在大鼠缺血性中风模型中的安全性。具体目标 6：召开 FDA IND 准备会议并收集用于提交缺血性中风干细胞治疗 IND 的文件。该提案扩展了我们确定干细胞治疗中风益处的科学平台。