TITLE:
Activin-Directed Differentiation of Human Embryonic Stem Cells Differentially Modulates Alveolar Epithelial Wound Repair via Paracrine Mechanism
AUTHORS:
Khondoker M. Akram, Monica A. Spiteri, Nicholas R. Forsyth
KEYWORDS:
Embryonic Stem Cells, Alveolar Epithelial Wound Repair, Idiopathic Pulmonary Fibrosis (IPF), Embryonic Stem Cell-Mediated Paracrine Mechanism, Activin-Directed hESC Differentiation
JOURNAL NAME:
Stem Cell Discovery,
Vol.4 No.3,
July
3,
2014
ABSTRACT: Differentiated embryonic
stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung
injury models; therefore, ESC, or their products, could be candidates for
regenerative therapy for incurable lung diseases, such as idiopathic pulmonary
fibrosis (IPF). In this study, we have investigated the paracrine effect of
differentiated and undifferentiated human ESC on alveolar epithelial cell (AEC)
wound repair. hESC line, SHEF-2 cells were differentiated with Activin treatment
for 22 days in an embryoid body (EB) suspension culture. Conditioned media (CM)
which contain cell secretory factors were collected at different time points of
differentiation. CM were then tested onin vitrowound repair model with human type II
AEC line, A549 cells (AEC). Our study demonstrated that CM originated from
undifferentiated hESC significantly inhibited AEC wound repair when compared to
the control. Whereas, CM originated from Activin-directed hESC differentiated
cell population demonstrated a differential reparative effect on AEC wound
repair model. CM obtained from Day-11 of differentiation significantly enhanced
AEC wound repair in comparison to CM collected from pre- and post-Day-11 of
differentiation. Day-11 CM enhanced AEC wound repair through significant
stimulation of cell migration and cell proliferation. RT-PCR and
immunocytochemistry confirmed that Day-11 CM was originated form a mixed
population of endodermal/mesodermal differentiated hESC. This report suggests a
putative paracrine-mediated epithelial injury healing mechanism by hESC
secreted products, which is valuable in the development of novel stem
cell-based therapeutic strategies.