Background: We previously reported the utility of engineered cell sheets composed of human islets and supporting cells in vitro and in vivo. It is unclear which type of supporting cell is most suitable for constructing cell sheets with human islets. The present study aimed to compare human fibroblasts, bone marrow–derived mesenchymal stem cells (BM–MSCs), and adipose–derived mesenchymal stem cells (ADSCs) as a supporting source for cell sheets.

Methods: Engineered cell sheets were fabricated with human islets using human fibroblasts, BM–MSCs, or ADSCs as supporting cells. The islet viability, recovery rate, glucose–stimulated insulin release (determined by the stimulation index), and cytokine secretion (TGF–β1, IL–6, and VEGF) of groups—including an islet–alone group as a control-were compared.

Results: All three sheet groups consistently exhibited higher viability, recovery rate, and stimulation index values than the islet-alone group. The ADSC group showed the highest viability and recovery rate among the three sheet groups. There were no discernible differences in the stimulation index values of the groups. The fibroblast group exhibited significantly higher TGF–β1 values in comparison to the other groups. The IL–6 level of the ADSC group was more than five times higher than that of the other groups. The ADSC group showed the VEGF level; however, it did not differ from that of the BM–MSC group to a statistically significant extent.

Conclusion: Engineered cell sheets composed of islets and supporting cells had a cytoprotective effect on islets. These results suggest that individual cell types could be a more attractive source for crafting engineered cell sheets in comparison to islets alone.

背景：我们先前报道了体外和体内由人胰岛和支持细胞组成的工程细胞片的实用性。尚不清楚哪种类型的支持细胞最适合与人胰岛一起构建细胞片。本研究旨在比较人类成纤维细胞，骨髓来源的间充质干细胞（BM–MSC）和脂肪来源的间充质干细胞（ADSC）作为细胞膜的支持来源。

方法：使用人成纤维细胞，BM-MSC或ADSC作为支持细胞，用人胰岛制备工程细胞片。比较了包括胰岛单独组作为对照组的各组的胰岛生存力，恢复率，葡萄糖刺激的胰岛素释放（由刺激指数确定）和细胞因子分泌（TGF-β1，IL-6和VEGF）。 。

结果：所有三个薄片组始终显示出比单独的胰岛组更高的生存力，恢复率和刺激指数值。在三个薄片组中，ADSC组显示出最高的生存力和恢复率。各组的刺激指数值无明显差异。与其他组相比，成纤维细胞组的TGF-β1值明显更高。ADSC组的IL-6水平比其他组高5倍以上。ADSC组显示VEGF水平。但是，它与BM-MSC组的差异无统计学意义。

结论：由胰岛和支持细胞组成的工程细胞片对胰岛具有细胞保护作用。这些结果表明，与单独的胰岛相比，单个细胞类型可能是制作工程化细胞片的更具吸引力的来源。