Effect of N-acetylcysteine on adipose-derived stem cell and autologous fat graft survival in a mouse model

Joshua Gillis, Simon Gebremeskel, Kyle D. Phipps, Lori A. Macneil, Christopher J. Sinal, Brent Johnston, Paul Hong, Michael Bezuhly

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Background: Autologous fat grafting is a popular reconstructive technique, but is limited by inconsistent graft retention. The authors examined whether a widely available, clinically safe antioxidant, N-acetylcysteine, could improve adipose-derived stem cell survival and graft take when added to tumescent solution during fat harvest. Methods: Inguinal fat pads were harvested from C57BL/6 mice using tumescent solution with or without N-acetylcysteine. Flow cytometric, proliferation, and differentiation assays were performed on isolated primary adipose-derived stem cells and 3T3-L1 preadipocytes treated with or without hydrogen peroxide and/or N-acetylcysteine. N-Acetylcysteine-treated or control grafts were injected under recipient mouse scalps and assessed by serial micro-computed tomographic volumetric analysis. Explanted grafts underwent immunohistochemical analysis. Results: In culture, N-acetylcysteine protected adipose-derived stem cells from oxidative stress and improved cell survival following hydrogen peroxide treatment. Combined exposure to both N-acetylcysteine and hydrogen peroxide led to a 200-fold increase in adipose-derived stem cell proliferation, significantly higher than with either agent alone. N-Acetylcysteine decreased differentiation of adipose-derived stem cells into mature adipocytes, as evidenced by decreased transcription of adipocyte differentiation markers and reduced Oil Red-O staining. In vivo, N-acetylcysteine treatment resulted in improved graft retention at 3 months compared with control (46 versus 17 percent; p = 0.027). N-Acetylcysteine-treated grafts demonstrated less fibrosis and inflammation, and a 33 percent increase in adipocyte density compared with controls (p < 0.001) that was not associated with increased vascularity. Conclusion: These findings provide proof of principle for the addition of N-acetylcysteine to tumescent harvest solution in the clinical setting to optimize fat graft yields.

Original languageEnglish
Pages (from-to)179e-188e
JournalPlastic and Reconstructive Surgery
Volume136
Issue number2
DOIs
Publication statusPublished - Aug 31 2015

Bibliographical note

Publisher Copyright:
© 2015 by the American Society of Plastic Surgeons.

ASJC Scopus Subject Areas

  • Surgery

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