Microsystems for Shaping Stem Cell Fate Selections

 描述：人类多能干细胞（hPSC）能够无限增殖，并可在人体内产生任何组织类型。有两种类型的hPSC-胚胎干细胞（ESC）和诱导多能干细胞（iPSC）。这些细胞可用作体外发育模型，并在再生医学应用中具有巨大的潜力。然而，广泛使用hPSC存在相当大的障碍，其中主要是复杂性和成本。复杂性源于维持多能性和高效地引导分化成所需谱系的困难。成本是由于依赖于昂贵的重组生长因子（GF）和其他试剂，在多周内大量使用。我们最近做了一个有趣的观察，干细胞以及成年细胞培养在微流控装置内没有灌注保留表型和功能显着优于标准培养皿中的细胞。进一步的研究表明，小体积的微流体室中的细胞上调内源性GF。基于这些观察，我们建议开发新的细胞培养微系统，利用细胞分泌的信号来维持和分化干细胞。总体影响：该项目旨在改变细胞培养的模式，从依赖外源性生长因子转向利用细胞自身的内源性信号。这将B

 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