TRANSPLANTATION OF MULTIPOTENT PROGENITOR CELLS 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）似乎具有使其高度适合作为干细胞疗法的性质。Athersys，Inc.拥有这些细胞的所有权我们最近与Athersys，Inc.建立了合作关系。该公司已经开发出了使这些细胞可用于临床的制造技术。Athersys，Inc.将为我们提供这些细胞。我们在啮齿动物中的初步数据表明，这些细胞作为中风的治疗方法是非常有前途的。为了开发这些细胞在中风中的效用，我们提出了一个翻译协议。所提出的一组实验将作为临床前基础，在缺血性中风患者中进行MFC移植。将检查在成人缺血性中风的啮齿动物模型中产生功效的可行性、安全性和中风后的最佳MFC剂量和移植时机。以下具体目标将作为里程碑，并有"可行和不可行"的标准。具体目标1：确定"长期"（即，移植后6个月）在短暂性大脑中动脉闭塞模型中IV大鼠MPC的功效。具体目的2：评价Athersys，Inc.生产的IV人MPC的长期疗效。根据GMP制造方案在GLP异种暂时性大脑中动脉闭塞模型中进行。具体目标3：评估IV人MPC在暴露于短暂性大脑中动脉闭塞模型的雄性和雌性以及成年和老年大鼠中实现长期行为益处的疗效。具体目的4：证明IV人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。具体目标五：表征同种异体大鼠MPC和异种人MPC中的干细胞组织相容性，以进一步提供IV MPC在大鼠缺血性卒中模型中的安全性。具体目标6：召开IND FDA准备会议，并收集用于提交缺血性卒中干细胞治疗IND的文件。这项建议扩展了我们的科学平台，以确定干细胞治疗中风的好处。

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.