Department of Biophysics, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
Acta Biochim Biophys Sin (Shanghai). 2012 Jun;44(6):463-75. doi: 10.1093/abbs/gms027. Epub 2012 May 3.
Presently, worldwide attempts are being made to apply stem cells and stem cell-derived products to a wide range of clinical applications and for the development of cell-based therapies. In order to harness stem cells and manipulate them for therapeutic application, it is very important to understand the basic biology of stem cells and identify the factors that govern the dynamics of these cells in the body. Several signaling pathways have emerged as key regulators of stem cells. Some of these signaling pathways regulate the stem cell's proliferative capacity and therefore act as direct regulators of the stem cell, whereas others are involved in shaping and maintaining the stem cell niche and therefore act as indirect regulators of the stem cell. It is difficult to identify which signaling pathways critically affect the stem cell's behavior and which are important for maintaining the quiescent population. A stem cell receives different extrinsic signals compared with the bulk population and responds to them differently. In order to manipulate these adult cells for therapeutic approaches it is crucial to identify how signaling pathways regulate stem cells either directly by regulating proliferative status or indirectly by influencing the niche. The main challenge is to identify whether different factors provide diverse extrinsic signals to the stem cell and its daughter cell population, or whether there are intrinsic differences in stem cell and daughter cell populations that is reflected in their behavior. In this study, we will focus on the various aspects of stem cell biology and differentiation, as well as exploring the potential strategies to intervene the differentiation process in order to obtain the desired yield of cells applicable in regenerative medicine.
目前,全世界都在努力将干细胞及其衍生产品应用于广泛的临床应用,并开发基于细胞的治疗方法。为了利用干细胞并对其进行操纵以用于治疗应用,了解干细胞的基本生物学并确定控制这些细胞在体内动态的因素非常重要。有几种信号通路已成为干细胞的关键调节剂。其中一些信号通路调节干细胞的增殖能力,因此它们是干细胞的直接调节剂,而其他信号通路则参与塑造和维持干细胞生态位,因此它们是干细胞的间接调节剂。很难确定哪些信号通路会严重影响干细胞的行为,哪些对维持静止细胞群体很重要。与大量群体相比,干细胞接收到不同的外在信号,并以不同的方式对其作出反应。为了将这些成体细胞用于治疗方法,必须确定信号通路如何通过调节增殖状态直接或通过影响生态位来调节干细胞。主要的挑战是确定不同的因素是否为干细胞及其子细胞群体提供不同的外在信号,或者干细胞和子细胞群体是否存在内在差异,从而反映在它们的行为中。在这项研究中,我们将重点关注干细胞生物学和分化的各个方面,以及探索潜在的策略来干预分化过程,以获得适用于再生医学的所需细胞产量。