Organ-specific ECM arrays for investigating cell-ECM interactions during stem cell differentiation
Organ-specific ECM arrays for investigating cell-ECM interactions during stem cell differentiation
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DOI：
10.1088/1758-5090/abc05f
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发表时间：
2021-01-01
期刊：
影响因子：
9
通讯作者：
Banerjee, Ipsita
中科院分区：
文献类型：
--
作者：
Goh, Saik-Kia;Halfter, Willi;Banerjee, Ipsita
多能干细胞是组织工程、再生医学和药物发现应用的有希望的细胞来源。干细胞分化的过程受到来自周围微环境的多参数提示的调节，其中一个关键的是细胞与细胞外基质（ECM）的相互作用。ECM是一种复杂的组织特异性结构，是干细胞功能和命运的重要生理调节因子。通过脱细胞组织/器官衍生的ECM最好地促进了这种天然ECM微环境生态位的重现，脱细胞组织/器官衍生的ECM可以忠实地再现生理环境，高保真于体内条件，并促进组织特异性细胞发育和成熟。认识到在3D培养环境中需要器官特异性ECM来驱动hPSC的表型分化和成熟，我们使用来自脱细胞器官（即胰腺、肝脏和心脏）的天然模拟ECM制造ECM阵列平台，其允许在2D和3D构型中的细胞-ECM相互作用。ECM阵列与快速定量成像集成，用于系统研究hPSC分化期间的基质蛋白谱和细胞-ECM相互作用的灵敏测量。我们通过阐明三种不同器官特异性ECM在支持hPSC的诱导胰腺分化中的作用来测试我们的平台。虽然本报告的重点是胰腺分化，但开发的平台是通用的，可用于表征任何谱系特异性分化。
Pluripotent stem cells are promising source of cells for tissue engineering, regenerative medicine and drug discovery applications. The process of stem cell differentiation is regulated by multi-parametric cues from the surrounding microenvironment, one of the critical one being cell interaction with extracellular matrix (ECM). The ECM is a complex tissue-specific structure which is an important physiological regulator of stem cell function and fate. Recapitulating this native ECM microenvironment niche is best facilitated by decellularized tissue/organ derived ECM, which can faithfully reproduce the physiological environment with high fidelity to in vivo condition and promote tissue-specific cellular development and maturation. Recognizing the need for organ specific ECM in a 3D culture environment in driving phenotypic differentiation and maturation of hPSCs, we fabricated an ECM array platform using native-mimicry ECM from decellularized organs (namely pancreas, liver and heart), which allows cell-ECM interactions in both 2D and 3D configuration. The ECM array was integrated with rapid quantitative imaging for a systematic investigation of matrix protein profiles and sensitive measurement of cell-ECM interaction during hPSC differentiation. We tested our platform by elucidating the role of the three different organ-specific ECM in supporting induced pancreatic differentiation of hPSCs. While the focus of this report is on pancreatic differentiation, the developed platform is versatile to be applied to characterize any lineage specific differentiation.