シグナル経路制御によるヒトES/iPS細胞からの肺胞細胞の誘導

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In an attempt to direct differentiation of hPSCs to the lung alveolar cells which are not restricted by technical considerations for the clinical application, various inhibitors and microenvironment factors which expected to participate in this developmental process have been assessed in current study based on developmental paradigms,We first tried to culture hPSCs with lung differentiation basal medium to make embryoid bodies. To enhance differentiation, three kinds of inhibitors (Wnt, BMP and ROCK). After further culturing the cells with inhibitors with growth factors (bFGF, Activin A) and TGFb inhibitors. Specification of the single cells of embryoid bodies to lung progenitor cells investigated using long culturing of single cells different concentration of various signal inhibitors including GSK3 inhibitors (Kenpaullone and CHIR99021), RA and cocktail of growth factors positively effect lung differentiation (FGF10, FGF7, BMP4, EGF) on fibronectin-coated plates, to probe the instructive mechanisms of endodermal lung differentiation.Because of the lack of time and terminating the project in its mid-stage, unfortunately we could not succeed to efficiently generate alveolar cells from hPSCs through evaluation of all possible signaling mechanisms that expected to regulate lung specification. Thus further study for elucidate other critical pathways in lung differentiation must used to understand the mechanisms of lung cells differentiation.However, a review paper has been prepared entitled ”Insights into the directed differentiation of hPSCs to lung differentiation”.