Enhancing Neurogenesis for Brain Tissue Regeneration

增强神经发生促进脑组织再生

基本信息

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
项目类别：
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

项目摘要

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够自发再生大脑组织，但这不会发生在哺乳动物中，尽管修复反应以神经发生增加。这种神经发生提供了细胞基质组织再生所需的。然而，组织再生也需要结构神经祖细胞可以整合并形成新组织的基质。我们有证明由细胞外基质（ECM）形成的生物支架可以实现这一点植入中风腔后发挥功能。然而，这个新的神经元密度形成组织太低，因此我们在此建议：1）建立最佳通过生长因子输送刺激神经发生的条件和2）利用这种增强的神经发生可以重新填充植入中风的 ECM 生物支架空腔。我们预计这种组合方法将增加新神经元的密度形成脑组织，这将导致行为功能的改善。一个 ECM 与神经发生刺激相结合的方法可能会提供一种新的方法慢性中风患者的治疗范例。目前尚无治疗方法解决这些患者组织空洞问题的干预措施。