Kirouac Daniel C, Zandstra Peter W
Institute of Biomaterials and Biomedical Engineering, Terrance Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Room 1116 11th Floor, 160 College Street, M5S 3E1 Toronto, Ontario, Canada.
Curr Opin Biotechnol. 2006 Oct;17(5):538-47. doi: 10.1016/j.copbio.2006.07.003. Epub 2006 Aug 8.
Efforts to develop culture technologies capable of eliciting robust human blood stem cell growth have met with limited success. Considering that adult stem cell cultures are complex systems, comprising multiple cell types with dynamically changing intracellular signalling environments and cellular compositions, this is not surprising. Typically treated as single-input single-output systems, adult stem cell cultures are better described as complex, non-linear, multiple-input multiple-output systems wherein the proliferation of subpopulations of cells leads to the formation of intercellular endogenously secreted protein interaction networks. Genomic and proteomic tools need to be applied to generate high-throughput (and ideally high-content) biological measurements of stem cell culture evolution. Datasets describing cellular interaction networks need to be integrated into predictive models of in vitro stem cell development. Ultimately, such models will serve as a starting point for the rational design of blood stem cell expansion bioprocesses utilizing dynamic system perturbations to achieve the preferential expansion of target cell populations.
开发能够引发强大人类血液干细胞生长的培养技术的努力取得的成功有限。鉴于成体干细胞培养是复杂的系统，由具有动态变化的细胞内信号环境和细胞组成的多种细胞类型构成，这并不令人惊讶。成体干细胞培养通常被视为单输入单输出系统，但更准确地说，它是复杂的、非线性的、多输入多输出系统，其中细胞亚群的增殖会导致细胞间内源性分泌蛋白相互作用网络的形成。需要应用基因组和蛋白质组学工具来生成关于干细胞培养进化的高通量（理想情况下是高内涵）生物学测量数据。描述细胞相互作用网络的数据集需要整合到体外干细胞发育的预测模型中。最终，这样的模型将作为合理设计血液干细胞扩增生物过程的起点，利用动态系统扰动来实现目标细胞群体的优先扩增。
