Human iPSC-derived mesenchymal stem cells (iMSCs) are an alternative to primary mesenchymal stem cells (MSCs), which have been a limited supply, and have attracted a great deal of interest as a promising cell source in cell-based therapy. However, despite their enormous therapeutic potential, it has been difficult to translate this potential into clinical applications due to the short viability duration of transplanted iMSCs. Therefore, to maximize the therapeutic effects of iMSCs, it is extremely important to extend their retention rate during and even after the transplantation. In this study, we developed a new extracellular matrix (ECM)-coating method involving the mild reduction of the cell surface. The reduction of disulfide bonds around the cell membrane enhanced the coating efficiency without a decrease in the viability and differentiation potential of iMSCs. We then induced ECM-coated single iMSCs to form three-dimensional spheroids via self-assembly of the aggregates within a physically confined microenvironment. The spheroids exhibited longer maintenance of the survival rate. Nanometric ECM coating of the cell membrane is a new approach as a key for resolving the conventional challenges of cell-based therapy.

中文翻译：

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三（2-羧乙基）膦介导的间充质干细胞纳米细胞外基质涂覆方法

人iPSC衍生的间充质干细胞（iMSCs）是原代间充质干细胞（MSCs）的替代品，后者的供应量有限，并且作为基于细胞的治疗中的有希望的细胞来源已引起了广泛的关注。然而，尽管它们具有巨大的治疗潜力，但由于移植的iMSC的生存期短，很难将这种潜力转化为临床应用。因此，为了使iMSC的治疗效果最大化，在移植期间甚至移植后延长其保留率极为重要。在这项研究中，我们开发了一种新的细胞外基质（ECM）涂层方法，涉及细胞表面的轻度减少。细胞膜周围二硫键的减少提高了包被效率，而不会降低iMSC的活力和分化潜能。然后，我们在物理受限的微环境中通过聚集体的自组装诱导ECM涂层的单个iMSC形成三维球体。球状体具有更长的存活率维持率。细胞膜的纳米级ECM涂层是一种新方法，是解决基于细胞疗法的传统挑战的关键。