Department of Biomedical Engineering, Thomas J. Watson School of Engineering and Applied Sciences, State University of New York in Binghamton, Binghamton, NY 13902, USA.
Int J Mol Sci. 2018 Nov 4;19(11):3459. doi: 10.3390/ijms19113459.
We have previously reported that a porous membrane of polyethylene terephthalate (PET) enables significant augmentation of human pluripotent stem cell (hPSC) proliferation and differentiation. The interaction between hPSCs and the PET surface induces β-catenin-mediated wingless/integrated () signaling, leading to upregulation of the expression of adhesion molecules in hPSCs. In this study, we sought to unveil mechanisms underlying the role of the PET membrane in hPSC self-renewal and metabolism. We discovered that physicochemical cues of the PET membrane considerably alter hPSC metabolism by increasing the cell yield and suppressing the generation of toxic byproduct, indicating an effective cell self-renewal and a less apoptotic culture environment in the membrane culture system. Furthermore, we discovered that a caspase-8 medicated apoptotic pathway plays a profound role in obstructing hPSCs grown on a traditional tissue culture plate (TCP). Treating hPSCs seeded on a TCP surface with a caspase-8 inhibitor significantly suppressed cellular apoptotic pathway and improved cell proliferation and metabolism. Our experimental results provided valuable insights into signal pathways influencing hPSC self-renewal during routine maintenance and expansion, which would shed light on large-scale preparation of hPSCs for clinical applications.
我们之前曾报道过，聚对苯二甲酸乙二醇酯（PET）的多孔膜可以显著促进人类多能干细胞（hPSC）的增殖和分化。hPSC 与 PET 表面的相互作用会诱导β-连环蛋白介导的 Wnt/β-联蛋白（）信号通路，从而上调 hPSC 中黏附分子的表达。在这项研究中，我们试图揭示 PET 膜在 hPSC 自我更新和代谢中的作用机制。我们发现，PET 膜的物理化学线索通过增加细胞产量和抑制有毒副产物的产生，极大地改变了 hPSC 的代谢，表明在膜培养系统中，细胞的自我更新是有效的，凋亡培养环境较少。此外，我们发现半胱天冬酶-8 介导的凋亡途径在阻止传统组织培养板（TCP）上生长的 hPSC 方面起着重要作用。用半胱天冬酶-8 抑制剂处理接种在 TCP 表面的 hPSC，可显著抑制细胞凋亡途径，促进细胞增殖和代谢。我们的实验结果为影响 hPSC 自我更新的信号通路提供了有价值的见解，这将为大规模制备 hPSC 用于临床应用提供依据。
