Thesis or Dissertation Differentiation of Mouse induced Pluripotent Stem Cells into Alveolar Epithelial Cells In Vitro for Use In Vivo

Zhou, Qiliang  ,  周, 启亮

pp.1 - 29 , 2015-03-23 , 新潟大学
学位の種類: 博士(医学). 報告番号: 甲第3978号. 学位記番号: 新大院博(医)甲第624号. 学位授与年月日: 平成27年3月23日
Stem Cells Translational Medicine. 2014, 3(6), 675-685.
Alveolar epithelial cells (AECs) differentiated from induced pluripotent stem cells (iPSCs) represent new opportunities in lung tissue engineering and cell therapy. In this study, we modified a two-step protocol for embryonic stem cells that resulted in a yield of ~9% SPC^+ alveolar epithelial type II (AEC II) cells from mouse iPSCs in a 12-day period. The differentiated iPSCs showed morphological characteristics similar to those of AEC II cells. When differentiated iPSCs were seeded and cultured in a mouse decellularized lung scaffold, the cells re-formed an alveolar structure and expressed SPC or T1α protein, markers of AEC II or AEC I cells, respectively. Finally, the differentiated iPSCs were instilled intratracheally into a bleomycin (BLM)-induced mouse acute lung injury model. The transplanted cells integrated into the lung alveolar structure and expressed SPC and T1α. Significantly reduced lung inflammation and decreased collagen deposition were observed following differentiated iPSC transplantation. In conclusion, we report a simple and rapid protocol for in vitro differentiation of mouse iPSCs into AECs. Differentiated iPSCs show potential for regenerating three-dimensional alveolar lung structure and can be used to abrogate lung injury.

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