TRANSPLANTATION OF MULTIPOTENT PROGENITOR CELLS IN STROKE

描述(由申请人提供)： 多能祖细胞(MFC)(自然，418：41-49,2002)是由明尼苏达大学的Veraillie博士和同事开发的，似乎具有使它们非常适合作为干细胞疗法的特性。Athersys，Inc.拥有这些电池的专有权利。我们最近与Athersys公司建立了合作关系，Athersys公司开发了制造技术，使这些细胞可用于临床。Athersys，Inc.将向我们提供这些电池。我们在啮齿动物身上的初步数据表明，这些细胞作为中风的治疗方法非常有希望。为了开发这些细胞在卒中中的作用，我们提出了一个翻译方案。拟议的一组实验将作为继续移植MFC治疗缺血性中风患者的临床前基础。在成人缺血性卒中的啮齿动物模型中，将检验卒中后MFC的最佳剂量和移植时机的可行性、安全性和最佳移植时机。以下具体目标将作为里程碑，并有“去和不去”的标准。具体目的1：在短暂性大脑中动脉闭塞模型上测定静脉注射大鼠骨髓基质细胞的“长期”(即移植后6个月)疗效。具体目的2：评价Athersys公司生产的IV型人MPC在GLP异种暂时性大脑中动脉闭塞模型中的长期疗效。具体目标3：评价静脉注射人MPC对雄性和雌性、成年和老年大鼠大脑中动脉短暂性闭塞模型的长期行为益处的影响。具体目标4：在永久性大脑中动脉结扎模型中，证明静脉注射人MPC对获得长期行为益处的有效性。具体目的5：鉴定异基因大鼠骨髓基质干细胞和异种人骨髓基质干细胞的组织相容性，进一步提供静脉注射骨髓基质干细胞在大鼠缺血性卒中模型中的安全性。具体目标6：召开IND FDA准备会议并收集文件，以提交IND用于缺血性中风的干细胞治疗。这项建议扩展了我们确定干细胞疗法在中风中的益处的科学平台。

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.