Electrostimulated bone marrow human mesenchymal stem cells produce follistatin.
OBJECTIVE
Follistatin (FST) and the related proteins FSTL1 and FSTL3 are crucial modulators of the transforming growth factor (TGF)-beta superfamily and function by neutralizing activins, a group of proteins implicated in many biologic processes, such as cell proliferation and differentiation, immune responses, various endocrine activities, wound repair, inflammation and fibrosis. Activins are increased in the serum of heart failure patients and in cardiomyocytes after experimental myocardial infarction, suggesting the involvement of activins in heart failure pathogenesis. FST is considered to be a key modulator in muscle development, differentiation and regeneration, and it has been implicated in the repair of mesodermal- and endodermal-derived tissues, promoting cell proliferation and hampering fibrogenesis. We have previously demonstrated that electrostimulation (ES) induces cardiomyocyte pre-commitment of both stem and non-stem cells in vitro. In this study, we evaluated whether applying ES to human mesenchymal stromal cells (hMSC) modulated FST production.


METHODS
hMSC were electrostimulated with 10 and 40 V for 12 h. FST production was assessed by immunostaining, Western blot and flow cytometry.


RESULTS
FST was up-regulated in hMSC after ES and was associated with cardiomyogenic differentiation of hMSC by short-term ES.


CONCLUSIONS
The possibility of stimulating the production of FST, a key regulator of mesodermal differentiation, in adult stem cells, while avoiding the drawbacks of conditioned media, dangerous drugs and gene delivery, has relevant potential therapeutic clinical applications. Additionally, this simple differentiation system could be useful for elucidating the molecular mechanisms driving the stem cell-differentiation process.
Genovese
Jorge A
JA
Cardiac and Molecular Biology Laboratory, Heart, Lung and Esophageal Surgery Institute, University of Pittsburgh Medical Center, Pittsburgh, USA. genoveseja@yahoo.com
Spadaccio
Cristiano
C
Rivello
Hernan Garcia
HG
Toyoda
Yoshiya
Y
Patel
Amit N
AN
D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology*; D002452:Cell Count; D002470:Cell Survival; D004558:Electric Stimulation; D038681:Follistatin / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D018613:Microscopy, Confocal
D038681:Follistatin