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.

摘要 脑组织的再生一直被认为是人类面临的最大挑战之一。 再生医学只有少数无脊椎动物能自发地再生大脑 组织，但这并不发生在哺乳动物中，虽然修复反应的形式， 神经发生增加。这种神经发生提供了 是组织再生所必需的然而，组织再生也需要结构性的 神经祖细胞可以整合并形成新组织的基质。我们有 证明了由细胞外基质（ECM）形成的生物支架起到了这一作用。 当植入中风腔时功能。然而，这个新的神经元密度 因此，我们在这里建议：1）建立最佳的组织， 通过生长因子递送刺激神经发生的条件，和2）利用 这增强了神经发生，以重新填充植入中风的ECM生物支架， 腔我们预计，这种结合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 联合ECM加神经发生刺激方法可能提供一种新的 慢性中风患者的治疗模式。目前，没有治疗 介入治疗可以解决这些患者的组织腔问题。