Transplantation of Multipotent Progenitor Cells in Stroke

中风多能祖细胞移植

基本信息

批准号：
7695963
负责人：
CESARIO V BORLONGAN
金额：
$ 70.05万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
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/7695963
关键词：
Adult Allogenic Animal Model Applications Grants Behavioral Bone Marrow Bone Marrow Stem Cell Cause of Death Cell Therapy Cells Clinical Condition Data Development Disease Dose Facilities and Administrative Costs Female Guanosine Monophosphate Histocompatibility Homing Human Immune Inflammatory Response Injury Intravenous Ischemic Stroke Legal patent Ligation MFC Marketing Mediating Medical Mesenchymal Stem Cells Middle Cerebral Artery Occlusion Minnesota Modeling Modification Multipotent Stem Cells Neurons Patients Pluripotent Stem Cells Population Preparation Primates Process Property Protocols documentation Rattus Recovery Rights Rodent Rodent Model Safety Series Site Stem cells Stroke Techniques Therapeutic Time Transplantation United States United States Food and Drug Administration United States National Institutes of Health Universities aged base cytokine disability human disease immunogenic innovation male middle cerebral artery post stroke pre-clinical preclinical study research study response stem stem cell therapy stroke therapy

项目摘要

Multipotent progenitor cells (MPCs), 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 MPCs in ischemic stroke patients. Feasibility, safety, and optimal MFC dose and transplantation timing poststroke 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.

多能祖细胞 (MPC)，由 Verfaillie 博士及其同事开发在明尼苏达大学，似乎具有使他们非常适合的特性作为干细胞疗法，Athersys, Inc. 最近拥有这些细胞的专有权利。与 Athersys, Inc. 建立了合作关系，后者开发了制造使这些细胞可用于临床的技术 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，我们提出了一个转化方案。一组实验将作为在中进行 MPC 移植的临床前基础缺血性中风患者的可行性、安全性以及最佳 MFC 剂量和中风后移植时机。将检查在成年缺血性中风的啮齿动物模型中产生功效的情况。遵循的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 大鼠的“长期”（即移植后 6 个月）功效暂时性大脑中动脉闭塞模型中的 MPC。 ¿具体目标 2：评估 Athersys, Inc. 生产的 IV 人类 MPC 的长期功效。根据 GLP 异种短暂中脑的 GMP 制造协议动脉闭塞模型。 ¿具体目标 3：评估 IV 人类 MPC 实现长期行为的功效短暂性中脑暴露对雄性和雌性、成年和老年大鼠的益处动脉闭塞模型。 ¿具体目标 4：展示 IV 人类 MPC 实现长期行为的功效永久性大脑中动脉结扎模型的优点。 ¿具体目标 5：表征同种异体大鼠 MPC 中的干细胞组织相容性和异种人类 MPC 进一步提供大鼠缺血性中风模型中 IV MPC 的安全性。 ¿具体目标 6：召开 IND FDA 准备会议并收集备案文件干细胞治疗缺血性中风的 IND。该提案扩展了我们确定干细胞治疗中风益处的科学平台。