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Modulation of vocal fold scar fibroblasts by adipose‐derived stem/stromal cells
Author(s) -
Kumai Yoshihiko,
Kobler James B.,
Park Hyoungshin,
Galindo Marilyn,
Herrera Victoria L.M.,
Zeitels Steven M.
Publication year - 2010
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.20753
Subject(s) - hepatocyte growth factor , stromal cell , adipose tissue , hyaluronic acid , chemistry , flow cytometry , stem cell , microbiology and biotechnology , andrology , pathology , biology , anatomy , medicine , biochemistry , receptor
Objectives/Hypothesis: To explore whether adipose‐derived stem/stromal cells (ASCs) have therapeutic potential for treating scarred superficial lamina propria through the effects of secreted hepatocyte growth factor (HGF) on scar fibroblasts. Study Design: In vitro study using coculture system. Methods: Scar fibroblasts (SFs) were isolated from ferret vocal folds electrocauterized 2 weeks previously. ASCs were isolated from ferret lipoaspirated subcutaneous abdominal fat. For coculture experiments, the two cell types were combined in Transwell plates for 6 days, followed by 1 or 3 days of monoculture after removing the upper chamber. Assays were then performed on cells and media from the bottom chamber. We measured: 1) the production of hyaluronic acid (HA), collagen and HGF via enzyme‐linked immunosorbent assays, 2) the expression of α‐smooth muscle actin (α‐SMA), 3) cell proliferation, and 4) apoptosis of SFs (2, 3, and 4 via flow cytometry). Other experiments examined the effects of HGF on SFs and the effects of HGF neutralization in the coculture system. Results: Coculture led to significant decreases in SF collagen production ( P < .05), cell proliferation ( P < .05), and α‐SMA expression ( P < .05), whereas HA production increased ( P < .05). Coculture also increased HGF secretion from ASCs ( P < .05). Neutralization of HGF abolished the inhibitory effects of ASCs on SF collagen synthesis ( P < .05). Conclusions: ASCs influence SFs to adopt a less fibrotic profile. It appears that HGF is at least one of the soluble factors responsible for this effect. Implanted ASCs could potentially ameliorate vocal fold scar by acting as long‐term, intrinsic sources of HGF. Laryngoscope, 2010