Abstract:
Human pluripotent stem cells (hPSCs), encompassing human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold immense potential in regenerative medicine, offering new opportunities for personalized cell therapies. However, their clinical translation is hindered by the inevitable reliance on xenogeneic components in culture environments. This study addresses this challenge by engineering a fully synthetic, xeno-free culture substrate, whose surface composition is tailored systematically for xeno-free culture of hPSCs. A functional polymer surface, pGC2 (poly(glycidyl methacrylate-grafting-guanidine-co-carboxylic acrylate)), offers excellent cell-adhesive properties as well as non-cytotoxicity, enabling robust hESCs and hiPSCs growth while presenting cost-competitiveness and scalability over Matrigel. This investigation includes comprehensive evaluations of pGC2 across diverse experimental conditions, demonstrating its wide adaptability with various pluripotent stem cell lines, culture media, and substrates. Crucially, pGC2 supports long-term hESCs and hiPSCs expansion, up to ten passages without compromising their stemness and pluripotency. Notably, this study is the first to confirm an identical proteomic profile after ten passages of xeno-free cultivation of hiPSCs on a polymeric substrate compared to Matrigel. The innovative substrate bridges the gap between laboratory research and clinical translation, offering a new promising avenue for advancing stem cell-based therapies.
摘要:
人多能干细胞(hPSC),包括人类胚胎干细胞(hESCs)和人类诱导多能干细胞(hiPSCs),在再生医学中拥有巨大的潜力,为个性化细胞治疗提供新的机会。然而,它们的临床翻译受到文化环境中对异种成分的不可避免的依赖。这项研究通过设计一种完全合成的,无异种培养基质,其表面组成被系统地定制用于hPSC的无异种培养。功能性聚合物表面,pGC2(聚(甲基丙烯酸缩水甘油酯-接枝-胍-共-羧酸丙烯酸酯)),提供优异的细胞粘附特性以及非细胞毒性,实现强劲的hESC和hiPSC增长,同时与Matrigel相比具有成本竞争力和可扩展性。这项调查包括在不同的实验条件下对pGC2的全面评估,证明了其对各种多能干细胞系的广泛适应性,文化媒介,和基底。至关重要的是,pGC2支持长期的hESC和hiPSC扩增,多达十个通道,而不损害其干性和多能性。值得注意的是,与Matrigel相比,这项研究首次证实了在聚合物底物上无异种培养hiPSC十次传代后相同的蛋白质组学谱。创新的基质弥合了实验室研究和临床翻译之间的差距,为推进基于干细胞的疗法提供了新的有希望的途径。