TRANSPLANTATION OF HUMAN BONE MARROW STROMAL CELLS

人骨髓基质细胞移植

• 批准号: 6785842
• 负责人: Itzhak Fischer
• 金额: $ 21.52万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6785842
• 关键词: bone marrow transplantation; cell differentiation; clinical research; disease /disorder model; gene delivery system; glia; human tissue; laboratory rat; nervous system disorder therapy; nervous system regeneration; neurons; nonhuman therapy evaluation; pluripotent stem cells; spinal cord injury; technology /technique development

DESCRIPTION (provided by applicant): This proposal is focused on application of recent advances in stem cell biology to a potential therapy for spinal cord injury. The proposed experiments will utilize mesenchymal stem cells derived from human bone marrow (marrow stromal cells, hMSCs), examine their phenotype following transplantation into spinal cord and test their ability to promote regeneration and recovery of function. Human MSCs are easy to obtain from a patient under local anesthesia, provide a renewal population and can be used for autologous grafting. Our preliminary data show that hMSCs grafted into spinal cord lesions survive, integrate well and appear to be permissive for axonal growth, and thus are excellent candidates for use in spinal core repair strategies. The full potential of hMSCs to differentiate is not well understood, but there is growing evidence that adult cells from bone marrow have remarkable plasticity and can assume diverse phenotypes dependent on the environment that they encounter. We reasoned that by transplanting hMSCs cells into spinal cord we can combine a systematic and direct examination of their fate in vivo with a detailed analysis of their therapeutic effects in neuronal rescue, axon regeneration and functional recovery in a well characterized model of spinal cord injury. Previous studies and our preliminary data suggest that hMSCs produce a variety of cytokines and neurotrophic factors that support survival and regeneration. The proposed experiments will examine the behavior of untreated and treated hMSCs in normal spinal cord (AIM 1) and in a well-characterized injury model of a unilateral C4 lesioned spinal cord (AIM 2). These cells will be analyzed with respect to their survival, migration and phenotype as well as their ability to rescue axotomized neurons (in the Red Nucleus), promote axon regeneration (of corticospinal and rubrospinal tracts) and restore function (using cylinder, rope and grid walking, reaching and patch removal tests). The therapeutic potential of different batches of hMSCs will then be correlated to their expression profile of secretory factors. In Aim 3 we will study the ability of grafted hMSCs to deliver therapeutic genes (BDNF and NT3) to the injured spinal cord and the effects of the genetic modification on the phenotypic properties of these cells and the potential for repair and restoration of function. Taken together, these experiments will provide a through preclinical analysis of the properties and therapeutic potential of hMSCs in the injured CNS.

描述（由申请人提供）： 该建议的重点是应用干细胞最新进展 生物学对脊髓损伤的潜在疗法。 提议 实验将利用源自人骨髓的间充质干细胞 （骨髓基质细胞，HMSC），检查其表型 将移植到脊髓中并测试其促进的能力 功能的再生和恢复。 人类MSC很容易从 患者在局部麻醉下，提供更新人群，可以使用 用于自体嫁接。 我们的初步数据表明，HMSC被嫁接到 脊髓病变生存，整合良好，似乎是允许的 轴突生长，因此是用于脊柱修复的出色候选者 策略。 HMSC的全部潜力分化不好 理解，但越来越多的证据表明骨髓的成年细胞 具有显着的可塑性，可以假设各种表型取决于 他们遇到的环境。 我们认为通过移植HMSC 细胞进入脊髓，我们可以结合系统的直接检查 他们在体内的命运，对他们的治疗作用进行了详细分析 井中的神经元救援，轴突再生和功能恢复 脊髓损伤的特征模型。 以前的研究和我们的 初步数据表明，HMSC会产生各种细胞因子，并且 支持生存和再生的神经营养因素。 提议 实验将检查未经处理和处理过的HMSC的行为 脊髓（AIM 1）和单方面特征良好的伤害模型 C4病变的脊髓（AIM 2）。 这些细胞将根据 他们的生存，迁移和表型以及救援能力 轴突化神经元（在红色核中），促进轴突再生（of 皮质脊髓和毛带脊髓）和恢复功能（使用气缸， 绳索和网格行走，到达和补丁测试）。治疗性 然后，不同批次的HMSC的潜力将与他们的 分泌因素的表达概况。 在AIM 3中，我们将研究能力 移植的HMSCs以将治疗基因（BDNF和NT3）传递到受伤的 脊髓和遗传修饰对表型的影响 这些细胞的特性以及修复和恢复的潜力 功能。 综上所述，这些实验将提供 HMSC中特性和治疗潜力的临床前分析 受伤的中枢神经系统。