MECHANISMS OF STEM CELL MIGRATION

描述 （改编自申请人摘要）组织工程对 细胞疗法的传递。 发现越来越多的 组织特异性干细胞的研究表明干细胞的重要性日益增加 在器官形成和组织工程中的应用。 因此，基本 了解器官发生的细胞命运过程 来源于组织特异性细胞将证明对生物学至关重要。 移植工程和细胞疗法的发展。 造血干 细胞（HSC）是最为人所知和研究的人类组织特异性干细胞 细胞 HSC在临床上通过移植用于挽救 通过重建造血组织功能的肌消融患者 来源于输入的干细胞。 因此，HSC移植 代表了干细胞的临床应用和改善移植物的需要， 工程虽然干细胞命运过程的基础知识。 的 一个实验室做出了两个与迁移有关的基本发现 ⑶ 34+细胞（在未成熟造血细胞上发现的表面标志物）;（A） 它们延伸出长（>100微米）的巨型脚，具有高度的动态性， 在引导这些细胞迁移中的作用;和（B）它们自发地和 在培养物中迅速（45分钟至2小时）聚集， 与趋化因子的分泌一致 因此 研究人员提出了一个研究计划，有两个具体目标，（1） 确定巨型足类的分子组成， 已知在细胞间作用的细胞骨架元件和表面标记物 通信;和（2）检查、纯化和鉴定趋化因子 从而诱导聚集过程。 这两个目标都将大大改善 对不成熟的迁移机制的理解 造血细胞 越来越多的组织特异性细胞 已经被描述，并且它们的器官功能的相似性导致 期望本提案的结果具有普遍性， 干细胞生物学的重要性和兴趣，因此将形成基础 用于新的生物移植工程

DESCRIPTION (Adapted from the applicant's abstract) Tissue engineering is critical to the delivery of cellular therapies. The discovery of an increasing number of tissue-specific stem cells points to the growing importance of stem cells in organogenesis and thus tissue engineering. Therefore, fundamental understanding of the cellular fate processes that underlie organogenesis originating from tissue-specific cells will prove critical to biological graft engineering and development of cellular therapies. Hematopoietic stem cells (HSCs) are the best known and studied human tissue specific stem cells. HSCs are clinically used through transplantation to rescue myoablated patents via the reconstruction of hematopoietic tissue function originating from the transfused stem cells. HSC transplantation thus represents the clinical use of stem cells and the need to improve graft engineering though fundamental knowledge of stem cell fate processes. The laboratory has made two fundamental discoveries that relate to the migration of CD34+ cells (a surface marker found on immature hematopoietic cells); (A) they extend long (>100 micron) megapods that are highly dynamic and play a role in guiding the migration of these cells; and (B) they spontaneously and rapidly (45 minutes to 2 hours) aggregate in culture in a fashion that is consistent with the secretion of a chemokine. Accordingly, the investigators propose a research program with two specific aims, (1) to determine the molecular makeup of the megapods, in terms of aggregate cytoskeletal elements and surface markers known to play a role in cell-cell communications; and (2) to examine, purify, and identify the chemokine(s) that induce the aggregation process. Both aims will significantly improve the understanding of the mechanisms that underlies the migration of immature hematopoietic cells. The increasing number of tissue- specific cells that have been described and the similarity in their organogenic functions lead to the expectation that the results of the present proposal are of general importance and interest in stem cell biology, and thus will form the basis for new biological graft engineering.