MECHANISMS OF STEM CELL MIGRATION

描述 (改编自申请者的摘要)组织工程对 细胞疗法的交付。不断增加的数量的发现 组织特异性干细胞的发现表明干细胞的重要性日益增长 器官发生，从而组织工程。因此，根本 对构成器官发生的细胞命运过程的理解 来自组织特异性细胞将被证明是生物学上的关键 移植工程和细胞疗法的发展。造血干 细胞(HSCs)是已知和研究最多的人类组织特异性干细胞。 细胞。造血干细胞通过移植在临床上的应用 重建造血组织功能的肌消融术患者 来源于输注的干细胞。因此，造血干细胞移植 代表了干细胞的临床应用和改进移植物的必要性 工程学，尽管对干细胞命运过程的基础知识。这个 实验室发现了两个与迁徙有关的基本发现 CD34+细胞(未成熟造血细胞上发现的一种表面标志)；(A) 它们延伸了长(&gt；100微米)的巨型足类，这些巨型足类具有高度的活力，并发挥着 在引导这些细胞迁移方面的作用；以及(B)它们自发地和 快速(45分钟至2小时)以一种 与趋化因子的分泌相一致。因此， 调查人员提出了一项有两个具体目标的研究计划，(1) 根据聚合体确定巨型足类的分子组成 已知在细胞-细胞中发挥作用的细胞骨架元素和表面标记 交流；以及(2)检查、提纯和鉴定趋化因子(S) 引发了聚合过程。这两个目标都将显著提高 对不成熟动物迁徙的机制的理解 造血细胞。越来越多的组织特异性细胞 以及它们在器官生成功能上的相似性导致 预期本提案的结果具有一般性 对干细胞生物学的重要性和兴趣，因此将形成基础 用于新的生物嫁接工程。

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.