• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Rapidly self-renewing stem cells in human bone marrow: The identification, characterization and regulation of a unique bone marrow stromal cell sub-population.
【24h】

Rapidly self-renewing stem cells in human bone marrow: The identification, characterization and regulation of a unique bone marrow stromal cell sub-population.

机译：人类骨髓中快速自我更新的干细胞：独特的骨髓基质细胞亚群的鉴定，表征和调节。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

It has been well demonstrated that the bone marrow contains a population of CD34+ hematopoietic stem cells (HSCs). However, the bone marrow also contains a second cell type, which meets most of the criteria for stem cells of non-hematopoietic tissues. Because of their multipotential differentiation capacity, these cells are currently known as mesenchymal stem cells or marrow stromal cells (MSCs). We have determined that cultures of human MSCs from different donors are heterogeneous showing varying growth and differentiation potentials. As samples were expanded in culture and approached senescence, they retained their ability to differentiate into osteoblasts. However, the cells failed to differentiate into adipocytes. The loss of multipotentiality after expansion presents a problem for MSC experimentation and their use as a therapeutic vehicle.; Three specific aims have been addressed in the following dissertation. The first specific aim was to develop a protocol for the expansion of MSCs in culture with an emphasis on distinguishing the most primitive cell type within the heterogeneous culture. The second aim was to identify the surface protein phenotype of the primitive MSC. Finally, the third aim was to determine the growth factors involved in MSC expansion in culture.; In this dissertation we have determined the conditions by which MSCs can be expanded 600–2000 fold in culture while maintaining their primitive attributes. This is an attractive characteristic for the use of MSCs as a therapeutic delivery vehicle. We have also identified a unique subset of human MSCs that are small, proliferate rapidly, undergo cyclical renewal, and are precursors of more mature cells in the primary culture. We have therefore termed these cells bone marrow derived, rapidly self-renewing stem (RS) cells. We have identified several protein epitopes (FLK-1, TRK, annexin II, transferrin receptor) that distinguish RS cells from mature cells and can be used to purify the RS cells from cultures of MSCs. We have also identified an autocrine/paracrine regulatory mechanism that regulates RS cell expansion and self-renewal in culture. These studies will ultimately allow for the exploitation of RS cells as a therapeutic delivery vehicle for cell and gene therapy.
机译：充分证明，骨髓中含有CD34 +造血干细胞（HSC）。但是，骨髓还含有第二种细胞类型，它满足非造血组织干细胞的大多数标准。由于它们的多能分化能力，这些细胞目前被称为间充质干细胞或骨髓基质细胞（MSC）。我们已经确定，来自不同供体的人MSC的培养物是异质的，显示出不同的生长和分化潜能。随着样品在培养物中的扩增和接近衰老，它们保留了分化为成骨细胞的能力。然而，细胞未能分化为脂肪细胞。扩增后失去多能性给MSC实验及其用作治疗载体带来了问题。以下论文提出了三个具体目标。第一个特定目标是开发一种用于在培养物中扩增MSC的协议，重点是区分异质培养物中最原始的细胞类型。第二个目的是鉴定原始MSC的表面蛋白表型。最后，第三个目标是确定涉及培养中MSC扩增的生长因子。在本文中，我们确定了在不改变其原始属性的前提下，MSCs可以在培养物中扩增600-2000倍的条件。这对于将MSC用作治疗递送载体是有吸引力的特征。我们还确定了人类MSC的独特子集，该子集很小，迅速增殖，经历周期性更新，并且是原代培养物中更成熟细胞的前体。因此，我们将这些细胞称为骨髓来源的快速自我更新干（RS）细胞。我们已经确定了几种蛋白质表位（FLK-1，TRK，膜联蛋白II，转铁蛋白受体），它们将RS细胞与成熟细胞区分开来，并可用于从MSC培养物中纯化RS细胞。我们还确定了一种自分泌/旁分泌调节机制，可调节RS细胞在培养中的扩增和自我更新。这些研究最终将允许利用RS细胞作为细胞和基因治疗的治疗性载体。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号