Differentiation of human amniotic fluid-derived mesenchymal stem cells into type II alveolar epithelial cells in vitro.

Type II alveolar epithelial cells (AECII) play a key role in maintaining normal alveolar homeostasis and repair. AECII derived from exogenous stem cells may provide novel treatment options for distal lung diseases. In this study, to explore whether amniotic fluid-derived mesenchymal stem cells (AFMSCs) may be induced to differentiate into AECII in vitro, AFMSCs were isolated from 15 independent samples of amniotic fluid, in which CD29, CD44, CD73, CD90, CD105 and CD166 were significantly expressed, but the expression of CD14, CD19, CD34 and CD45 was negative. Octamer-binding transcription factor 4 (OCT4) at both the mRNA and protein level was also significantly expressed in the AFMSCs. We demonstrate that AFMSCs cannot be induced to differentiate into AECII using KnockOut™ serum replacement (KOSR) only. Surfactant protein (SP)A and SPC mRNA expression in the differentiated AFMSCs was significantly induced by the appropriate combination of KOSR, activin A and small airway basal medium (SABM). However, SPA and SPC expression was negative with an inappropriate induction. Lamellar bodies were observed only in the cells which were appropriately induced by KOSR, activin A and SABM. Thus, these results indicate that AFMSCs may be induced to differentiate into AECII-like cells in vitro with the use of the appropriate induction medium, including KOSR, activin A and SABM, suggesting that that AFMSCs have the potential for use in lung regenerative therapy.