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: 9215666
• 负责人: Alexander Revzin
• 金额: $ 35.78万
• 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/9215666
• 关键词: Adult; Area; Automobile Driving; COS Cells; Cell Culture System; Cell Culture Techniques; Cell Line; Cells; Coculture Techniques; Complex; Cultured Cells; Data; Devices; Diffuse; Endoderm Cell; Ensure; Fibroblasts; Growth Factor; Hepatic; Hepatocyte; Human; Human body; Investigation; Maintenance; Microfluidic Microchips; Microfluidics; Organ; Perfusion; Phenotype; Production; Protocols documentation; Reagent; Recombinant Growth Factor; Regenerative Medicine; Reproducibility; Resort; Seeds; Shapes; Signal Induction; Signal Pathway; Signal Transduction; Source; Stem cells; Testing; Time; TimeLine; Tissues; cost; design; embryonic stem cell; experimental study; fascinate; human embryonic stem cell; human pluripotent stem cell; human stem cells; improved; in vitro Model; induced pluripotent stem cell; microsystems; model development; morphogens; novel; penis foreskin; pluripotency; prevent; public health relevance; small molecule inhibitor; stellate cell; stem cell differentiation; stem cell fate; tool

 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