FIBRIN BASED SCAFFOLDS FOR SPINAL CORD INJURY

用于脊髓损伤的纤维蛋白支架

• 批准号: 8464811
• 负责人: Shelly Elese Sakiyama-Elbert
• 金额: $ 31.44万
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8464811
• 关键词: Acute; Address; Adult; Age; Amyotrophic Lateral Sclerosis; Biocompatible Materials; Caring; Cell Adhesion; Cell Fraction; Cell Line; Cell Transplantation; Cells; Chondroitin ABC Lyase; Clinical; Combined Modality Therapy; Cues; Development; Drug Delivery Systems; Environment; Erinaceidae; Fiber; Fibrin; Future; Glycolates; Goals; Grant; Green Fluorescent Proteins; Growth Factor; In Vitro; Incidence; Individual; Injury; Kinetics; Knowledge; Microspheres; Modeling; Motor Neurons; Mus; Natural regeneration; Nature; Nerve Regeneration; Neuraxis; Neurites; Neurodegenerative Disorders; Neurons; Neurotrophin 3; Oligodendroglia; Pain; Patients; Peptides; Pharmaceutical Preparations; Population; Productivity; Protocols documentation; Puromycin; Quality of life; Recovery of Function; Resistance; Signal Transduction; Site; Sonic Hedgehog Pathway; Spinal Cord; Spinal Cord Lesions; Spinal cord injury; Spinal cord injury patients; Stimulus; Testing; Therapeutic; Time; Tissues; Transplantation; Tretinoin; United States; allodynia; base; cost; embryonic stem cell; improved; in vivo; prevent; progenitor; public health relevance; receptor; relating to nervous system; response; scaffold; spinal cord regeneration; transcription factor; tumor

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.

描述(由申请人提供)：本提案的统一假设是，生物材料支架的使用对于开发成功的脊髓损伤治疗方法至关重要。在缺乏能够帮助修复损伤部位的生物材料支架的情况下，损伤脊髓中缺乏促进再生的底物，限制了目前药物输送和细胞移植方法的有效性。我们推测，这种生物材料支架可以用于指导胚胎干细胞来源的前体运动神经元(PMN)的分化，提供生长因子营养信号，并提供药物来克服成年脊髓的抑制性质。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检验，所有这些目标都是实现脊髓再生的目标所必需的。这项建议的目的是：(1)测试假设，从纤维蛋白为基础的生物材料支架输送生长因子将使胚胎干细胞衍生的祖细胞运动神经元(PMN)在体外存活并分化为运动神经元，其水平与传统分化方案观察到的水平相当或更好。(2)在亚急性(14天)脊髓损伤的体内实验中，验证这样一种假说：与单纯的PMN移植(无支架)相比，从纤维蛋白为基础的生物材料支架可以增强胚胎干细胞来源的运动神经元前体细胞(PMN)的存活和向运动神经元的分化。(3)验证这样一种假设，即生物材料支架(与生长因子输送)、细胞移植和药物输送相结合以克服成人脊髓的抑制信号，将提供一种能够在亚急性(14天)脊髓损伤后实现再生的组合疗法。

项目成果

Stem cells for spinal cord injury: Strategies to inform differentiation and transplantation.

• DOI: 10.1002/bit.26074
• 发表时间: 2017-03
• 期刊: Biotechnology and bioengineering
• 影响因子: 3.8
• 作者: Iyer NR;Wilems TS;Sakiyama-Elbert SE
• 通讯作者: Sakiyama-Elbert SE

Incorporation of heparin into biomaterials.

• DOI: 10.1016/j.actbio.2013.08.045
• 发表时间: 2014-04
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Sakiyama-Elbert, Shelly E.

Sustained dual drug delivery of anti-inhibitory molecules for treatment of spinal cord injury.

• DOI: 10.1016/j.jconrel.2015.06.031
• 发表时间: 2015-09-10
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Wilems TS;Sakiyama-Elbert SE
• 通讯作者: Sakiyama-Elbert SE

Tissue-engineered fibrin scaffolds containing neural progenitors enhance functional recovery in a subacute model of SCI.

• DOI: 10.1039/c0sm00173b
• 发表时间: 2010-10-21
• 期刊: Soft matter
• 影响因子: 3.4
• 作者: Johnson PJ;Tatara A;McCreedy DA;Shiu A;Sakiyama-Elbert SE
• 通讯作者: Sakiyama-Elbert SE

Engineering peripheral nerve repair.

• DOI: 10.1016/j.copbio.2013.05.006
• 发表时间: 2013-10
• 期刊: CURRENT OPINION IN BIOTECHNOLOGY
• 影响因子: 7.7
• 作者: Marquardt, Laura M.;Sakiyama-Elbert, Shelly E.
• 通讯作者: Sakiyama-Elbert, Shelly E.