Microsystems for Shaping Stem Cell Fate Selections

用于塑造干细胞命运选择的微系统

• 批准号: 9412328
• 负责人: Alexander Revzin
• 金额: $ 6.32万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9412328
• 关键词: Microsystems; Shaping; Stem; Cell; Fate

 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

 描述：人类多能干细胞 (hPSC) 能够无限增殖，可产生人体内的任何组织类型。 hPSC 有两种类型：胚胎干细胞 (ESC) 和诱导多能干细胞 (iPSC)。细胞可用作体外发育模型，并在再生医学应用中具有巨大潜力。然而，hPSC 的广泛使用存在相当大的障碍，其中主要是复杂性和成本。其原因是难以维持多能性并高效地定向分化为所需的谱系，这是由于对昂贵的重组生长因子（GF）和其他试剂在数周内大量使用造成的。在没有灌注的微流体装置内培养的干细胞以及成体细胞保留的表型和功能明显优于标准培养器皿中的细胞。进一步研究表明，小体积微流体室内的细胞上调内源性。基于这些观察，我们建议开发新型细胞培养微系统，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，摆脱对外源生长因子的依赖。并利用细胞自身的内源信号。