FIBRIN BASED SCAFFOLDS FOR SPINAL CORD INJURY

描述（由申请人提供）：该提案的统一假设是，生物材料支架的使用对于脊髓损伤成功治疗的发展至关重要。在缺乏可以帮助桥接损伤部位的生物材料支架的情况下，损伤的脊髓中缺乏再生促进基质限制了当前药物递送和细胞移植方法的功效。我们假设，生物材料支架可用于指导胚胎干细胞衍生的前体运动神经元（pMNs）的分化，目前的生长因子营养线索，并提供药物，以克服抑制性的成人脊髓。通过使用生物材料支架，我们假设，我们将能够提出必要的联合治疗，以实现脊髓损伤后的显着再生。这一假设将通过解决以下具体目标进行系统测试，所有这些都是实现脊髓再生目标所必需的。 该提议的目的是：（1）检验以下假设：从基于纤维蛋白的生物材料支架递送生长因子将使得胚胎干细胞衍生的祖细胞运动神经元（pMN）在体外环境中以与传统分化方案所观察到的水平相当或更好的水平存活并分化为运动神经元。(2)在亚急性（14天）脊髓损伤的体内环境中，与单独的pMN移植（无支架）相比，从基于纤维蛋白的生物材料支架递送生长因子将能够增强胚胎干细胞衍生的运动神经元祖细胞（pMN）的存活和分化为运动神经元。(3)为了检验生物材料支架（具有生长因子递送）、细胞移植和药物递送的组合以克服成人脊髓的抑制性线索将提供能够在亚急性（14天）脊髓损伤后实现再生的组合疗法的假设。

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 bridge the injury site, the lack of regeneration promoting substrates in the injured spinal cord limits the efficacy of current drug delivery and cell transplantation approaches. We hypothesize that the biomaterial scaffolds can be used to direct the differentiation of embryonic stem cell-derived progenitor motor neurons (pMNs), present growth factor trophic cues and deliver drugs to overcome the inhibitory nature of the adult spinal cord. Through the use of a biomaterial scaffold we hypothesize that we will be able to present combination therapies necessary 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 growth factor delivery from a fibrin-based biomaterial scaffold will enable the survival and differentiation of embryonic stem cell-derived progenitor motor neurons (pMNs) into motoneurons in an in vitro setting at levels comparable to or better than that observed with traditional differentiation protocols. (2) To test the hypothesis that growth factor delivery from a fibrin-based biomaterial scaffold will enable enhanced survival and differentiation of embryonic stem cell-derived motoneuron progenitors (pMNs) into motoneurons compared with pMN transplantation alone (no scaffold) in the in vivo setting of sub-acute (14 day) spinal cord injury. (3) To test the hypothesis that the combination of a biomaterial scaffold (with growth factor delivery), cell transplantation, and delivery of drugs to overcome the inhibitory cues of the adult spinal cord, will provide a combination therapy that is able to achieve regeneration following sub-acute (14 day) spinal cord injury.