MR Imaging of Bioscaffold-Induced Neural Progenitor Migration

生物支架诱导的神经祖细胞迁移的磁共振成像

• 批准号: 10273779
• 负责人: Michel M. Modo
• 金额: $ 41.44万
• 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: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10273779
• 关键词: Adult; Anatomy; Brain; Cells; Characteristics; Complex; Contrast Media; Control Groups; Data; Date of birth; Detection; Development; Engineering; Ensure; Extracellular Matrix; Fluorescence Microscopy; Gadolinium; Generations; Histologic; Histology; Hydrogels; Imaging Device; Immunohistochemistry; Implant; Infarction; Injections; Injury; Invaded; Label; Lateral; Magnetic Resonance Imaging; Mammals; Maps; Methods; Modification; Natural regeneration; Neurons; Noise; Outcome; Play; Process; Regenerative Medicine; Resolution; Role; Route; Signal Transduction; Site; Source; Specificity; Speed; Stroke; Testing; Time; Tissues; Up-Regulation; Visualization; adult neurogenesis; analytical tool; bioscaffold; brain cell; brain tissue; cell motility; design; experimental study; histological studies; implantation; improved; in vivo; in vivo imaging; insight; lateral ventricle; migration; nanoGold; nerve stem cell; neurogenesis; novel; novel strategies; preimplantation; relating to nervous system; response; spatiotemporal; stem cells; subventricular zone; tissue regeneration; tool

Abstract The regeneration of brain tissue has been considered one of the greatest challenges for regenerative medicine. Implantation of an extracellular matrix (ECM) hydrogel can produce de novo brain tissue by attracting endogenous neural progenitors into a tissue cavity. These neural progenitors originate in the subventricular zone (SVZ), one of the few neurogenic sites in the adult brain. Initially, neural progenitors migrate in the peri-infarct- damaged tissue before invading the bioscaffold. However, little is known about the route or time-course of migration of these cells. The objective of this application is to develop a non-invasive MR imaging paradigm that affords the tracking of neural progenitors from the SVZ to the bioscaffold. Specifically, we here aim to: 1) develop and optimize contrast agent to label endogenous neural progenitor cells, 2) to non-invasively track the migration of neural progenitors and 3) to determine the temporal dynamics of neural progenitors responding to a hydrogel implant. Achieving an in vivo visualization of neural progenitor migrations will aid us to understand the contribution of neurogenesis to brain tissue regeneration, but also to devise novel strategies that can manipulate this process.

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。 再生医学细胞外基质（ECM）水凝胶的植入可以 通过将内源性神经祖细胞吸引到组织中来重新产生脑组织 腔这些神经祖细胞起源于室管膜下区（SVZ）， 成年人大脑中的神经源性部位。最初，神经祖细胞迁移到梗塞周围， 在侵入生物支架之前破坏组织。然而，人们对路线知之甚少 或这些细胞迁移的时间过程。此应用程序的目标是开发一个 非侵入性磁共振成像模式，提供神经祖细胞的跟踪， SVZ到生物支架。具体而言，我们的目标是：1）开发和优化造影剂 标记内源性神经前体细胞，2）非侵入性地追踪 神经前体细胞和3）确定神经前体细胞的时间动态 对水凝胶植入物的反应。实现神经祖细胞的体内可视化 迁移将帮助我们了解神经发生对脑组织的贡献 再生，但也设计新的策略，可以操纵这一过程。