Combination strategies to promote repair and functional recovery following stroke

促进中风后修复和功能恢复的组合策略

• 批准号: 549672-2020
• 负责人: Morshead, CindiM
• 金额: $ 13.4万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Collaborative Health Research Projects
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=750826
• 关键词: Combination; strategies; promote; repair; functional

In Canada, it is estimated that stroke costs the Canadian economy almost $3 billion per year.Stem cell based therapies hold great promise for the treatment of stroke. This research willlay the foundation for clinical approaches to treat stroke by addressing current challenges withcell based therapies. Our team of researchers and industry partner will take advantage ofinnovations in stem cell biology, cell transplantation, and bioengineering to promote bothtissue and functional repair in preclinical models of stroke. Our measures of success arefunctional assays undoubtedly the most relevant outcome for translation. Wewill perform our studies in chronic stroke models, as chronic stroke has been less well studieddespite the serious impacts including premature death, poor quality of life and large adverseeconomic effects on families, communities and society in general. With the goal of developingclinically relevant strategies to treat the stroke-injured brain we will combine a novel,proprietary human cell source engineered by our industry partner, that permits patient specificcells to be used for cell transplantation. These cells are outside of ethical concerns and ableto avoid rejection after transplantation. Importantly, the cells are designed to only make brainspecific cells so will not form inappropriate cell types following transplantation. We willcombine the cell transplantation with novel bioengineered tools to deliver drugs that promotebrain plasticity and cell survival by reducing the negative environmental factors found in theinjured brain. Further, to enhance cell survival - a significant challenge for cell basedtherapies - our preclinical studies will utilize a novel, patented drug that inhibits cell death.Together, these preclinical studies using combinatorial strategies will set the stage for clinicaltrials to treat stroke.

在加拿大，据估计，中风每年给加拿大经济造成近 30 亿美元的损失。基于干细胞的疗法为中风的治疗带来了巨大的希望。这项研究将为通过细胞疗法解决当前挑战来治疗中风的临床方法奠定基础。我们的研究人员和行业合作伙伴团队将利用干细胞生物学、细胞移植和生物工程方面的创新来促进中风临床前模型中的组织和功能修复。我们衡量成功的标准是功能分析，这无疑是与翻译最相关的结果。我们将在慢性中风模型中进行研究，因为尽管慢性中风具有严重影响，包括过早死亡、生活质量差以及对家庭、社区和整个社会产生巨大的不利经济影响，但对慢性中风的研究还较少。为了开发临床相关策略来治疗中风损伤的大脑，我们将结合由我们的行业合作伙伴设计的新型专有人类细胞源，允许将患者特定细胞用于细胞移植。这些细胞不存在伦理问题，并且能够避免移植后的排斥反应。重要的是，这些细胞被设计为仅产生脑特异性细胞，因此在移植后不会形成不合适的细胞类型。我们将细胞移植与新型生物工程工具相结合，通过减少受损大脑中发现的负面环境因素来提供促进大脑可塑性和细胞存活的药物。此外，为了提高细胞存活率（细胞疗法的一项重大挑战），我们的临床前研究将利用一种抑制细胞死亡的新型专利药物。 总之，这些使用组合策略的临床前研究将为治疗中风的临床试验奠定基础。