Fibrin-based scaffolds for spinal cord injury

用于脊髓损伤的纤维蛋白支架

• 批准号: 7013656
• 负责人: Shelly Elese Sakiyama-Elbert
• 金额: $ 27.64万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7013656
• 关键词: bioengineering /biomedical engineering; biomaterial development /preparation; biomaterial evaluation; biotechnology; blood brain barrier; cell differentiation; cell migration; central neural pathway /tract; embryonic stem cell; evoked potentials; fibrin; flow cytometry; immunocytochemistry; laboratory rat; molecular probes; nervous system regeneration; neurons; neurotrophic factors; oligodendroglia; spinal cord injury; stem cell transplantation; terminal nick end labeling; tissue /cell culture; tissue support frame

DESCRIPTION (provided by applicant): The unifying hypothesis of this proposal is that the use of biomaterial scaffolds is critical to the development of successful therapies for spinal cord injury. In the absence of a biomaterial scaffold that can help to bridge the injury site, the lack of regeneration promoting substrates in the injured spinal cord limits the efficacy of growth factor delivery and cell transplantation approaches. We hypothesize that controlled release of growth factors over a prolonged period of time (weeks) from a fibrin-based biomaterial scaffold alone or in combination with embryonic stem cell-derived neural lineage cells (ESNLCs) is needed to achieve significant regeneration following spinal cord injury. This hypothesis will be tested systematically by addressing the following specific aims, all of which are necessary to achieve the goal of spinal cord regeneration. The aims of this proposal are: (1) To test the hypothesis that a fibrin-based biomaterial scaffold enables sufficient controlled release of growth factor (neurotrophin-3) to enable enhanced short and long-term regeneration compared to uncontrolled growth factor release in a rat spinal cord injury model. (2) To test the hypothesis that growth factor delivery from a fibrin-based biomaterial scaffold will enable survival and differentiation of embryonic stem cell-derived neural lineage cells (ESNLCs) into neurons in an in vitro setting comparable to or better than that observed with traditional differentiation protocols. (3) To test the hypothesis that growth factor delivery from a fibrin-based biomaterial scaffold will enable enhance survival and differentiation of embryonic stem cell-derived neural lineage cells (ESNLCs) into neurons compared with ESNLCs alone (no scaffold) in vivo in the setting of spinal cord injury.

描述（由申请人提供）：该提案的统一假设是，使用生物材料支架对于开发成功的脊髓损伤疗法至关重要。在没有生物材料支架的情况下，可以帮助桥接损伤部位，缺乏再生促进受伤的脊髓中的底物限制了生长因子递送和细胞移植方法的疗效。我们假设在长时间（几周）中，单独使用基于纤维蛋白的生物材料支架或与胚胎干细胞衍生的神经谱系细胞（ESNLC）结合使用的长期释放生长因子的控制释放，以实现脊髓索后的重大再生。该假设将通过解决以下特定目标来系统地检验，所有这些目标对于实现脊髓再生的目标都是必要的。该提案的目的是：（1）检验以下假设：基于纤维蛋白的生物材料支架能够充分控制生长因子（Neurotrophin-3），以使与大鼠脊髓损伤模型中不受控制的生长因子释放相比增强了短期和长期再生。 （2）测试以下假设：从基于纤维蛋白的生物材料支架的生长因子递送将使胚胎干细胞衍生的神经谱系细胞（ESNLC）的生存和分化与与传统差异方案相当的体外环境中的神经元的生存和分化。 （3）为了测试以下假设：与单独的ESNLC相比，与单独的ESNLC相比，在脊髓脊髓损伤的情况下，与单独的ESNLC相比，与单独的ESNLC相比，从基于纤维蛋白的生物材料支架递送将增强胚胎干细胞衍生的神经谱系细胞（ESNLC）的生存和分化为神经元。