Immunomodulatory Hydrogels for Stem Cell Therapy after TBI

用于 TBI 后干细胞治疗的免疫调节水凝胶

• 批准号: 8466393
• 负责人: Ravi V. Bellamkonda
• 金额: $ 31.64万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-15 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8466393
• 关键词: Address; Affect; Allogenic; American; Anti-Inflammatory Agents; Anti-inflammatory; Apoptosis; Axon; Behavioral; Cell Death; Cell Survival; Cell Therapy; Cell Transplantation; Cell Transplants; Cells; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Clinical; Clinical Management; Cognitive; Complex; Development; Edema; Environment; Experimental Models; Gel; Health; Human; Hydrogels; Immune; Impairment; In Situ; Individual; Inflammation; Injury; Mediating; Modeling; Molecular; Motor; Natural Killer Cells; Nature; Neurologic; Neurophysiology - biologic function; Neurosurgeon; Organ Transplantation; Outcome; Patients; Procedures; Qualifying; Quality of life; RNA Interference; Relative (related person); Reporting; Research; Research Personnel; Rodent; Rodent Model; Site; Stem cells; T-Lymphocyte; Testing; Therapeutic; Tissues; Transplantation; Trauma; Traumatic Brain Injury; Treatment Efficacy; Tumor Necrosis Factor Ligand Superfamily Member 6; Veterans; body system; brahma; cohort; design; effective therapy; engineering design; experience; improved; in vivo; innovation; nerve injury; nerve stem cell; novel; relating to nervous system; repaired; sertoli cell; small molecule; statistics; stem; stem cell therapy

DESCRIPTION (provided by applicant): The center for disease control reports that 1.7 million Americans suffer traumatic brain injuries, half a million of whom are children. Clinical management of traumatic brain injury (TBI) is challenging due to the complexity of the injury as well as due to the paucity of effective treatment options. Due to the complex nature of the injury involving inflammation, cell loss and edema, cell therapies may be necessary as small molecular anti-inflammatory or neuroprotective strategies have not been very successful. Specifically stem cell therapy has the potential to significantly improve outcomes after TBI. However, one major impediment to successful neural stem cell (NSC) therapy is their poor survival after transplantation due to host T cells and Natural Killer (NK) cell mediated apoptosis of transplanted NSCs. Here, we propose to design and engineer in situ gelling hydrogel carriers for NSCs such that they confer immune-privilege for a period of days to weeks in vivo. We propose to exploit the Fas-ligand mediated cell death of T cells and NK cells to generate an immune privilege zone for NSCs. We posit that enhancing NSC survival is a critical and necessary condition to evaluating NSC therapy's potential for treating TBI. Our aims are designed to design the appropriate hydrogel carriers for NSC, test their ability to promote NSC survival in vivo in an experimental model of TBI, and finally investigate whether indeed enhanced NSC survival results in motor and cognitive improvement in a rodent model of TBI relative to untreated cohorts. Successful completion of the proposed studies would have significant impact on improvement of the quality of life of individuals with TBI, and have implications for stem cell therapies in other organ systems.

描述（由申请人提供）：疾病控制中心报告说，有170万美国人遭受创伤性脑损伤，其中一百万是儿童。由于损伤的复杂性以及由于有效的治疗选择的匮乏，脑外伤（TBI）的临床管理（TBI）是具有挑战性的。由于涉及炎症，细胞丧失和水肿的损伤的复杂性，因此可能需要细胞疗法，因为小分子抗炎或神经保护策略并不是很成功。特异性干细胞疗法有可能在TBI后显着改善预后。然而，成功的神经干细胞（NSC）治疗的一个主要障碍是由于宿主T细胞和天然杀手（NK）细胞介导的移植NSC凋亡而导致移植后的存活不良。在这里，我们建议在NSC上设计和设计原位凝胶水凝胶载体，以便它们在体内赋予免疫特你几天至几周。我们建议利用T细胞和NK细胞的FAS-配体介导的细胞死亡，以生成NSC的免疫特权区域。我们认为，增强NSC生存是评估NSC治疗治疗TBI潜力的关键和必要条件。我们的目标旨在设计适当的水凝胶载体以用于NSC，测试其在TBI实验模型中促进体内NSC存活的能力，最后研究在未经处理的同类群体相对于未经处理的TBI的啮齿动物模型中，NSC的生存是否确实会导致运动和认知改善。成功完成拟议的研究将对改善TBI个体生活质量的改善产生重大影响，并对其他器官系统中的干细胞疗法产生影响。