Enhancing Neurogenesis for Brain Tissue Regeneration

增强神经发生促进脑组织再生

• 批准号: 10217654
• 负责人: Michel M. Modo
• 金额: $ 42.3万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217654
• 关键词: Address; Adult; Ambystoma; Animals; Area; Behavioral; Brain; Brain Injuries; Cells; Data; Dose; Epidermal Growth Factor; Extracellular Matrix; Family; Goals; Growth Factor; Implant; Infarction; Infusion procedures; Injury; Invaded; Invertebrates; Length; Lesion; Mammals; Natural regeneration; Neurons; Outcome; Patients; Performance; Pump; Quality of life; Recovery; Regenerative Medicine; Short Interspersed Nucleotide Elements; Source; Stroke; Structure; Testing; Therapeutic; Therapeutic Intervention; Tissues; Translating; adult neurogenesis; behavioral impairment; behavioral outcome; betacellulin; bioscaffold; body system; brain cell; brain tissue; chronic stroke; clinical translation; density; design; experimental study; implantation; improved; improved outcome; lateral ventricle; member; nerve stem cell; neurogenesis; novel therapeutics; repaired; response; restoration; stroke patient; subcutaneous; subventricular zone; tissue regeneration; tissue repair

ABSTRACT The regeneration of brain tissue has been considered one of the greatest challenges for regenerative medicine. Only a few invertebrate species spontaneously regenerate brain tissue, but this does not occur in mammals, although a repair response in form of an increased neurogenesis occurs. This neurogenesis provides the cellular substrate required for tissue regeneration. However, tissue regeneration also requires a structural substrates where neural progenitors can integrate and form new tissue. We have demonstrated that bioscaffolds formed out of extracellular matrix (ECM) serve this function when implanted into a stroke cavity. Nevertheless, neuron density in this newly forming tissue is too low and we therefore here propose to: 1) establish optimal conditions for neurogenesis stimulation through growth factor delivery and 2) to exploit this enhanced neurogenesis to re-populate an ECM bioscaffold implanted into the stroke cavity. We expect that this combined approach will increase neuron density in the newly forming brain tissue and this will lead to an improved outcome of behavioral functions. A combined ECM plus neurogenesis stimulation approach can potentially provide a new treatment paradigm for chronic stroke patients. At present, there is no therapeutic intervention that addresses the issue of a tissue cavity in these patients.

抽象的 脑组织的再生已被认为是最大的挑战之一 再生医学。只有少数无脊椎动物自发再生大脑 组织，但这并不是在哺乳动物中发生的，尽管以 神经发生增加。这种神经发生提供了细胞底物 组织再生所必需的。但是，组织再生也需要结构性 神经祖细胞可以整合并形成新组织的底物。我们有 证明是由细胞外基质（ECM）形成的生物施加剂。 植入中风腔时功能。然而，这个新的神经元密度 形成组织太低，因此我们在这里建议：1）建立最佳 通过生长因子递送刺激神经发生的条件，2）利用 这种增强的神经发生，重新填充了植入中风 腔。我们希望这种合并的方法将增加新的神经元密度 形成脑组织，这将导致行为功能的改善。一个 结合ECM加神经发生刺激方法可以潜在地提供新的 慢性中风患者的治疗范例。目前，没有治疗性 处理这些患者组织腔问题的干预措施。