Introduction

Mesenchymal stem cells (MSCs) are promising candidates for cell therapy owing to their therapeutic effect in various diseases. In general, MSCs grow efficiently in serum-containing culture media, indicating an essential role of adhesion in their mesenchymal lineage-specific propagation. Nevertheless, the use of non-human supplements in culture (xeno-free issue) in addition to the lack of control over unknown factors in the serum hampers the clinical transition of MSCs.

Methods

In this study, embryonic stem cell derived mesenchymal stem cells (ES-MSCs) were used owing to their scalable production, and they expressed a series of MSC markers same as adipose-derived MSCs. The affinity of the culture matrix was increased by combining fibronectin coating with its adjuvant peptide, gelatin, or both (FNGP) on tissue culture polystyrene to compare the regenerative, therapeutic activities of ES-MSCs with a cell binding plate as a commercial control.

Results

The FNGP culture plate promoted pivotal therapeutic functions of ES-MSCs as evidenced by their increased stemness as well as anti-inflammatory and proangiogenic effects in vitro. Indeed, after culturing on the FNGP plates, ES-MSCs efficiently rescued the necrotic damages in mouse ischemic hindlimb model.

Conclusions

This study suggests a potential solution by promoting the surface affinity of culture plates using a mixture of human fibronectin and its adjuvant PHSRN peptide in gelatin. The FNGP plate is expected to serve as an effective alternative for serum-free MSC expansion for bench to clinical transition.

中文翻译：

---

纤连蛋白与 PHSRN 肽在明胶混合物中的协同粘附促进人 ES 衍生的 MSCs 的治疗潜力。

介绍

间充质干细胞（MSCs）因其在各种疾病中的治疗作用而成为细胞治疗的有希望的候选者。一般来说，MSCs 在含血清培养基中有效生长，表明粘附在其间充质谱系特异性增殖中的重要作用。然而，除了缺乏对血清中未知因素的控制外，在培养中使用非人类补充剂（无异源问题）阻碍了 MSCs 的临床转化。

方法

在本研究中，胚胎干细胞来源的间充质干细胞 (ES-MSCs) 因其可扩展的生产而被使用，它们表达了与脂肪来源的 MSCs 相同的一系列 MSC 标志物。通过在组织培养聚苯乙烯上将纤连蛋白涂层与其佐剂肽、明胶或两者 (FNGP) 结合来增加培养基质的亲和力，以比较 ES-MSCs 与作为商业对照的细胞结合板的再生、治疗活性。

结果

FNGP 培养板促进了 ES-MSCs 的关键治疗功能，这从它们增加的干性以及体外抗炎和促血管生成作用得到证明。事实上，在 FNGP 板上培养后，ES-MSCs 有效地挽救了小鼠缺血后肢模型中的坏死损伤。

结论

这项研究提出了一种潜在的解决方案，即通过使用人纤连蛋白及其在明胶中的 PHSRN 佐剂肽的混合物来提高培养板的表面亲和力。FNGP 板有望作为无血清 MSC 扩增的有效替代品，用于实验室向临床过渡。