Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8654, Japan.
Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan.
Cells. 2021 Aug 7;10(8):2017. doi: 10.3390/cells10082017.
The production of functional islet-like cells from human-induced pluripotent stem cells (hiPSCs) is a promising strategy for the therapeutic use and disease modeling for type 1 diabetes. However, the production cost of islet-like cells is extremely high due to the use of expensive growth factors for differentiation. In a conventional culture method, growth factors and beneficial autocrine factors remaining in the culture medium are removed along with toxic metabolites during the medium change, and it limits the efficient utilization of those factors. In this study, we demonstrated that the dialysis suspension culture system is possible to reduce the usage of growth factors to one-third in the differentiation of hiPSC-derived endocrine progenitor cells to islet-like cells by reducing the medium change frequency with the refinement of the culture medium. Furthermore, the expression levels of hormone-secretion-related genes and the efficiency of differentiation were improved with the dialysis suspension culture system, possibly due to the retaining of autocrine factors. In addition, we confirmed several improvements required for the further study of the dialysis culture system. These findings showed the promising possibility of the dialysis suspension culture system for the low-cost production of islet-like cells.
从人诱导多能干细胞(hiPSCs)中产生功能性胰岛样细胞是治疗 1 型糖尿病和疾病建模的有前途的策略。然而,由于分化过程中使用昂贵的生长因子,胰岛样细胞的生产成本极高。在传统的培养方法中,在更换培养基时,生长因子和培养基中残留的有益自分泌因子会与有毒代谢物一起被去除,这限制了这些因子的有效利用。在这项研究中,我们证明了通过改进培养基,减少换液频率,透析悬浮培养系统可以将 hiPSC 衍生的内分泌祖细胞向胰岛样细胞分化过程中生长因子的使用量减少到三分之一。此外,透析悬浮培养系统还可以提高激素分泌相关基因的表达水平和分化效率,这可能是由于自分泌因子的保留。此外,我们还证实了进一步研究透析培养系统所需的几个改进。这些发现表明,透析悬浮培养系统具有胰岛样细胞低成本生产的广阔前景。