Enhancing Neurogenesis for Brain Tissue Regeneration

摘要 脑组织的再生一直被认为是 再生医学。只有少数几种无脊椎动物能自发再生大脑 组织，但这种情况在哺乳动物中不会发生，尽管修复反应的形式是 神经发生增多。这种神经发生提供了细胞底物 是组织再生所必需的。然而，组织再生也需要结构上的 神经前体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)形成的生物支架可以满足这一要求 植入中风腔后即可发挥功能。然而，这个新生的神经元密度 组织形成率太低，因此我们在此建议：1)建立最佳 生长因子传递刺激神经发生的条件和2)开发 这增强了神经发生以重新填充植入卒中的ECM生物支架 空洞。我们预计这种结合的方法将增加新生的 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有可能提供一种新的 慢性卒中患者的治疗模式。目前，还没有治疗方法。 解决这些患者的组织空洞问题的干预。

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.