Ethanol alters the osteogenic differentiation of amniotic fluid-derived stem cells.
BACKGROUND
Fetal alcohol spectrum disorder (FASD) is a set of developmental defects caused by prenatal alcohol exposure. Clinical manifestations of FASD are highly variable and include mental retardation and developmental defects of the heart, kidney, muscle, skeleton, and craniofacial structures. Specific effects of ethanol on fetal cells include induction of apoptosis as well as inhibition of proliferation, differentiation, and migration. This complex set of responses suggests that a bioinformatics approach could clarify some of the pathways involved in these responses.


METHODS
In this study, the responses of fetal stem cells derived from the amniotic fluid (AFSCs) to treatment with ethanol have been examined. Large-scale transcriptome analysis of ethanol-treated AFSCs indicates that genes involved in skeletal development and ossification are up-regulated in these cells. Therefore, the effect of ethanol on osteogenic differentiation of AFSCs was studied.


RESULTS
Exposure to ethanol during the first 48 hours of an osteogenic differentiation protocol increased in vitro calcium deposition by AFSCs and increased alkaline phosphatase activity. In contrast, ethanol treatment later in the differentiation protocol (day 8) had no significant effect on the activity of alkaline phosphatase.


CONCLUSIONS
These results suggest that transient exposure of AFSCs to ethanol during early differentiation enhances osteogenic differentiation of the cells.
Hipp
Jennifer A
JA
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Hipp
Jason D
JD
Atala
Anthony
A
Soker
Shay
S
D000469:Alkaline Phosphatase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D053686:Fetal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D053495:Osteopontin / Q000378:metabolism; D011247:Pregnancy
D053495:Osteopontin; D000431:Ethanol; D000469:Alkaline Phosphatase; D002118:Calcium