Transplantation of Multipotent Progenitor Cells in Stroke

中风多能祖细胞移植

• 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
• 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

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.

由Verfaillie博士及其同事开发的多态祖细胞（MPC） 在明尼苏达大学，似乎具有使其非常合适的财产 作为干细胞疗法。 Athersys，Inc。拥有这些细胞的专有权利。我们最近有 与Athersys，Inc。建立了合作关系，该关系已经开发了制造业 使这些细胞可用于临床使用的技术。 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。在 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。提议 一组实验将作为继续移植MPCS的临床前基础 缺血性中风患者。可行性，安全性和最佳MFC剂量和移植时机卒中后 为了在成年缺血性中风的啮齿动物模型中产生效率。这 遵循特定的目标将作为里程碑，并具有“ GO和No-Go”标准。 »特定目的1：确定静脉大鼠的“长期”（即移植后6个月） 瞬时脑动脉闭塞模型中的MPC。 »特定目标2：评估Athersys，Inc。生产的IV人类MPC的长期效率。 根据GMP制造方案，GLP异构瞬态中间大脑 动脉闭塞模型。 »特定目的3：评估IV人类MPC实现长期行为的效率 男性和女性的益处，以及暴露于短暂性中大脑的成年和老年大鼠 动脉闭塞模型。 »特定目的4：证明IV人类MPC实现长期行为的效率 永久性大脑中动脉连接模型的好处。 »特定目标5：表征同种异体大鼠MPC中的干细胞组织兼容性和 异种人MPC在大鼠缺血性中风模型中进一步提供IV MPC的安全性。 »特定目标6：进行IND FDA准备会议和组装文件 缺血性中风中干细胞疗法的IND。 该建议扩展了我们的科学平台，以确定干细胞疗法在中风中的益处。