Neural differentiation potential of USSC in vitro and in vivo

USSC 体外和体内的神经分化潜力

• 批准号: 55928142
• 负责人: Professor Dr. Kurt Gottmann
• 金额: --
• 依托单位: Institut für Neurobiologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/55928142?language=en
• 关键词: Neural; differentiation; potential; USSC; vitro

Implantation of unrestricted somatic stem cells derived from human umbilical cord blood (USSC) represents a potential strategy for cell therapies of neurodegenerative diseases or CNS injury. In this project we will investigate the potential of USSC to improve axonal regeneration and functional (locomotor) recovery in rat models of traumatic spinal cord injury (SCI). In our preliminary work we could demonstrate that local implantation of USSC into injured thoracic spinal cord and migration of the grafted cells into the lesion zone led to substantially enhanced axon growth and significant locomotor improvement as revealed by several established behavioural tests (open field, gridwalk, CatWalk). In this project we will (i) characterize fiber tract-specific reactions following USSC grafting into the injured spinal cord, (ii) analyze neuroprotective responses including tissue sparing and retrograde rescue of cortical neurons, (iii) determine cell dosage, timing (acute vs. subacute) and route (local vs. systemic) of USSC application to optimize axon regeneration and functional outcome in SCI, (iv) identify potential regeneration-promoting proteins secreted by USSC using a differential proteome (secretome) approach in collaboration with A4, (v) infuse selected neurite growth-promoting USSC-CM factors to prove the paracrine support of USSC in SCI, (vi) include spinal contusion as a second clinically more relevant type of injury and (vii) further compare USSC with human mesenchymal stem cells (MSC) in spinal cord repair.

人脐血来源的无限制体细胞移植是神经退行性疾病或中枢神经系统损伤的一种潜在的细胞治疗策略。在这个项目中，我们将研究USSC在促进创伤性脊髓损伤(SCI)大鼠模型的轴突再生和功能(运动)恢复方面的潜力。在我们的初步工作中，我们可以证明，USSC局部植入受损的胸髓，并将移植细胞迁移到损伤区，如几个已建立的行为测试(旷场、网格行走、T台步)所显示的那样，显著促进了轴突生长和显著的运动改善。在这个项目中，我们将(I)描述USSC移植到受损脊髓后的纤维束特异性反应，(Ii)分析神经保护反应，包括组织保留和皮质神经元的逆行拯救，(Iii)确定USSC的细胞剂量、应用时机(急性和亚急性)和途径(局部和全身)以优化脊髓损伤中的轴突再生和功能结果，(Iv)使用差异蛋白质组(分泌组)方法与A4合作识别USSC分泌的潜在再生促进蛋白，(V)注入精选的促进轴突生长的USSC-CM因子以证明USSC在脊髓损伤中的旁分泌支持，(Vi)将脊髓挫伤列为第二种临床上更相关的损伤类型，以及(Vii)进一步比较USSC和人骨髓间充质干细胞(MSC)在脊髓修复中的作用。