Crosstalk between adipose-derived stem/stromal cells and vocal fold fibroblasts in vitro.
OBJECTIVE
To explore adipose-derived stem cell/fibroblast interactions as a potential remodeling pathway for vocal fold scar.


METHODS
Fibroblasts and adipose-derived stem/stromal cells (ASCs) were cultured alone and in combination in a cell-contact-independent paracrine system. Analyses of cell proliferation, and the production of hyaluronic acid (HA) and collagen were performed on samples collected on days 1, 3, and 7.


METHODS
Normal fibroblasts (NFs) were isolated bilaterally from the subepithelial lamina propria of two normal ferret vocal folds. Scar fibroblasts (SFs) were isolated from vocal folds that were electrocauterized 2 weeks before harvest. ASCs were isolated from lipoaspirated subcutaneous abdominal fat of two ferrets. A transwell cell-contact-independent cell communication culturing system was used for coculture experiments. Cells were seeded at 50,000/well in both monoculture and coculture experiments.


RESULTS
In monoculture, SFs proliferated faster and produced less HA and more collagen than NFs at day 7 (P < .05). In SF/ASC coculture, SF proliferation was diminished and collagen production at day 7 decreased (P < .05). HA production did not differ between monoculture and coculture conditions.


CONCLUSIONS
Normal and scar-tissue-derived vocal fold fibroblasts maintain phenotypic differences in culture, thus validating this in vitro scar model. In co-culture, contact-independent crosstalk occurs between SFs and ASCa, leading to less collagen secretion. The data support the hypothesis that ASCs can induce favorable remodeling of scarred vocal folds in vivo by their interactions with endogenous fibroblasts.
Kumai
Yoshihiko
Y
Department of Surgery, Harvard Medical School, Center for Laryngeal Surgery and Voice Rehabilitation, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Kobler
James B
JB
Park
Hyoungshin
H
Lopez-Guerra
Gerardo
G
Karajanagi
Sandeep
S
Herrera
Victoria L M
VL
Zeitels
Steven M
SM
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D018920:Coculture Techniques; D003094:Collagen / Q000096:biosynthesis; D004195:Disease Models, Animal; D055664:Electrochemical Techniques / Q000592:standards; D005289:Ferrets; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D006820:Hyaluronic Acid / Q000096:biosynthesis; D020239:Receptor Cross-Talk; D013234:Stem Cells / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*; D014827:Vocal Cords / Q000166:cytology* / Q000601:surgery
D006820:Hyaluronic Acid; D003094:Collagen