Microsystems for Shaping Stem Cell Fate Selections

 描述：人类多能干细胞(HPSCs)能够无限增殖，并可在人体内分化为任何组织类型。有两种类型的hPSCs-胚胎干细胞(ESCs)和诱导多能干细胞(IPSCs)。这些细胞可能被用作体外发育模型，并具有巨大的再生医学应用潜力。然而，hPSC的广泛使用存在相当大的障碍，其中最主要的是复杂性和成本。复杂性源于维持多能性和高效地引导分化为理想的谱系的困难。成本I是由于依赖昂贵的重组生长因子(GFS)和其他试剂在数周内大量使用所致。我们最近做了一项有趣的观察，在微流控设备中培养的干细胞以及成体细胞在没有灌流的情况下保持了比标准培养中的细胞更好的表型和功能。进一步的研究发现，小体积微流体室内的细胞正在上调内源性GFS。在这些观察的基础上，我们建议开发新的细胞培养微系统，该系统将利用细胞分泌的信号来维持和分化干细胞。总体影响：该项目旨在将细胞培养的范式从依赖外源生长因子转变为利用细胞自身的内源信号。这将是

 DESCRIPTION: Human pluripotent stem cells (hPSCs) are capable of unlimited proliferation and may give rise to any tissue type in the human body. There are two types of hPSCs - embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). These cells may be used as in vitro models of development and hold enormous potential for regenerative medicine applications. However, there are considerable roadblocks to widespread use of hPSCs, chief among which are complexity and cost. Complexity arises from the difficulty in maintaining pluripotency and directing differentiation into desirable lineages with high efficiency. The cost i due to reliance on expensive recombinant growth factors (GFs) and other reagents used in copious amounts over multiple weeks. We have recently made a fascinating observation that stem cells as well as adult cells cultured inside microfluidic devices without perfusion retained phenotype and function significantly better than cells in standard cultureware. Further investigation revealed that cells inside small volumes of microfluidic chambers were upregulating endogenous GFs. Building on these observations, we propose to develop novel cell culture microsystems that will harness cell-secreted signals for maintenance and differentiation of stem cells. Overall impact: This project aims to shift the paradigm of cell cultre away from reliance on exogenous growth factors and towards harnessing cells' own endogenous signals. This will b