Vitamin D3 (calcitriol) Improves Autologous Fat Graft Retention In A Murine Model
Marisa J. DeSanto, BS1, Sheri Wang, BS2, Lei Chen3, Alexander G. Stavros, BS2, Jeffrey A. Gusenoff, MD4, J. Peter Rubin, MD4, Lauren E. Kokai, PhD4.
1Ohio University Heritage College of Osteopathic Medicine, Athens, OH, USA, 2University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, 3Department of Plastic Surgery, University of Pittsburgh; First Affiliated Hospital of Fujian Medical University: Fuzhou, Pittsburgh; Fujian , China, PA, USA, 4Department of Plastic Surgery, University of Pittsburgh; McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Vitamin D3 (Calcitriol) Improves Autologous Fat Graft Retention in a Murine Model
Marisa DeSanto, BS1; Sheri Wang, BS2; Lei Chen,3,4; Alexander G Stavros, BS2; Jeffrey A Gusenoff, MD3,5; J. Peter Rubin, MD3,5; Lauren E Kokai, PhD3,5.
1. Ohio University Heritage College of Osteopathic Medicine.
2. University of Pittsburgh School of Medicine.
3. Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
4. First Affiliated Hospital of Fujian Medical University: Fuzhou, Fujian , China
5. McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA
INTRODUCTION: Autologous fat grafting is an important technique in plastic surgery that is currently limited by unpredictable or unsatisfactory outcomes. After injection, adipose grafts experience hypoxia-induced necrosis, inflammation, macrophage-resorption and finally, repopulation by circulating cells. We hypothesize that reducing phagocytic clearance of the residual graft scaffold will increase overall retention following revascularization. Calcitriol, the active form of Vitamin D3, decreases inflammation and promotes adipogenesis, therefore we compared fat grafting with local and systemic calcitriol to control fat grafting outcomes in an animal model.
METHODS: Coleman processed lipoaspirate from 3 unique donors was implanted bilaterally on the mouse dorsum and graft retention and viability were assessed at 1, 4, and 12 weeks. Calcitriol was either delivered systemically by thrice weekly calcitriol IP injections or locally by introducing calcitriol into the lipoaspirate container for 1 hour. To determine mechanism of action, in vitro experiments were performed with adipose particles suspended in media with calcitriol in 1% hypoxic culture and tissue viability and gene expression were measured.
RESULTS: At 1 and 4 weeks, both local and systemic administration of calcitriol increased graft retention (p<0.05). At 12 weeks, systemic calcitriol increased retention from 54.6% to 79.8% (p<0.05) while local delivery was not significantly different from the control. At every study time point, there was no significant difference in the H&E based injury score between groups, however perilipin IHC showed adipocyte viability was increased at 12 weeks from 48.7% to 63.3% (local p>0.05) and from 48.3 to 70.7% (systemic, p<0.05). In vitro, calcitriol decreased the expression of inflammatory cytokines corresponding to phagocytotic activity and M1 activity (SOD1, IFNγ, IL6) and increased expression of apoptosis genes (BNIP3). Surprisingly, our results suggested that Calcitriol obviated necrosis-related inflammation through induction of apoptosis, resulting in decreased inflammation, decreased fibrosis and improved tissue regeneration.
CONCLUSION: Calcitriol, an FDA-approved drug with known immunomodulatory properties, appears to be a promising drug for improving long term fat grafting outcomes. Calcitriol demonstrated the ability to increase fat graft retention up to 12 weeks in mice and exhibited anti-inflammatory properties in vitro. Calcitriol has potential as a simple, economical means of increasing fat graft retention.
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