Prowse Andrew B J, Chong Fenny, Gray Peter P, Munro Trent P
The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, St Lucia, QLD, 4072, Australia.
Stem Cell Res. 2011 Jan;6(1):1-12. doi: 10.1016/j.scr.2010.09.005. Epub 2010 Oct 7.
Use of stem cells, whether adult or embryonic for clinical applications to treat diseases such as Parkinson's, macular degeneration or Type I diabetes will require a homogenous population of mature, terminally differentiated cells. A current area of intense interest is the development of defined surfaces for stem cell derivation, maintenance, proliferation and subsequent differentiation, which are capable of replicating the complex cellular environment existing in vivo. During development many cellular cues result from integrin signalling induced by the local extracellular matrix. There are 24 known integrin heterodimers comprised of one of 18 α subunits and one of 8 β subunits and these have a diverse range of functions mediating cell-cell adhesion, growth factor receptor responses and intracellular signalling cascades for cell migration, differentiation, survival and proliferation. We discuss here a brief summary of defined conditions for human embryonic stem cell culture together with a description of integrin function and signalling pathways. The importance of integrin expression during development is highlighted as critical for lineage specific cell function and how consideration of the integrin expression profile should be made while differentiating stem cells for use in therapy. In addition this review summarises the known integrin expression profiles for human embryonic stem cells and 3 common adult stem cell types: mesenchymal, haematopoietic and neural. We then outline some of the possible technologies available for investigating cell-extracellular matrix interactions and subsequent integrin mediated cell responses.
将干细胞(无论是成体干细胞还是胚胎干细胞)用于临床治疗帕金森氏症、黄斑变性或I型糖尿病等疾病,都需要获得大量成熟的、终末分化的同质细胞群体。目前一个备受关注的领域是开发特定的表面,用于干细胞的衍生、维持、增殖及后续分化,这些表面能够复制体内存在的复杂细胞环境。在发育过程中,许多细胞信号来自局部细胞外基质诱导的整合素信号传导。已知有24种整合素异二聚体,由18种α亚基之一和8种β亚基之一组成,它们具有多种功能,介导细胞间黏附、生长因子受体反应以及细胞迁移、分化、存活和增殖的细胞内信号级联反应。在此,我们简要概述人类胚胎干细胞培养的特定条件,并描述整合素的功能和信号通路。整合素在发育过程中的表达对于谱系特异性细胞功能至关重要,这一点得到了强调,同时还阐述了在将干细胞分化用于治疗时应如何考虑整合素表达谱。此外,本综述总结了人类胚胎干细胞以及3种常见成体干细胞类型(间充质干细胞、造血干细胞和神经干细胞)已知的整合素表达谱。然后,我们概述了一些可用于研究细胞与细胞外基质相互作用以及随后整合素介导的细胞反应的可能技术。