Systemic administration of adipose-derived stromal cells concurrent with fat grafting

Background: Cell-assisted lipotransfer (CAL), a technique involving free fat grafting mixed with adipose-derived stromal cells (ASCs), has gained popularity for enhancing fat graft retention. In terms of stem cell delivery, intravenous injection can be a novel alternative with clinical value. However, the effects of intravenously injected ASCs concurrent with fat grafting have not been described. We investigated the histologic and microenvironmental changes in grafted fat when ASCs were intravenously injected concurrent with grafting. Methods: Using a modified animal model of CAL, adipose tissue from GFP-expressing C57BL/6J (B6) mice was grafted into recipient wild-type B6 mice, followed by intravenous injection of ASCs from DsRed-expressing B6 mice. The distribution of ASCs was evaluated using bioluminescent imaging and graft volume was measured using micro-computed tomography scans. Donor fat and ASCs were traced using immunofluorescent staining. Results: We identified the recruitment of ASCs inside the graft after intravenous injection of ASCs concurrent with grafting despite the arrest of cells in the lungs. Intravenous injection of ASCs resulted in significantly higher adipogenesis gene expression, retention of graft volume, and vascular density of the graft. A tracing study performed until postoperative week 8 revealed that intravenously injected ASCs mainly induced angiogenesis and adipogenesis by paracrine action rather than direct differentiation. Conclusions: Consistent with results of CAL, ASC supplementation by systemic administration led to improved retention of the fat graft. The findings broaden the surgical options for fat grafting and enhance the clinical value of CAL. * The first two authors contributed equally to this study. Ung Sik Jin, M.D., Ph.D. , Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Phone: 82-2-2072-2370, Fax: 82-2-3675-7792, E-mail: usj1011@snu.ac.kr Financial disclosures: The authors have no financial or institutional interest in any of the drugs, materials, or devices described in this article. Acknowledgement: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2017R1A2B1006403 to Hak Chang and NRF-2018R1C1B6004618 to Il-Kug Kim). Statement on IACUC approval: Animal care and experimental procedures were approved by the Institutional Animal Care and Use Committee (No. 17-0163-S1A1) of Seoul National University Hospital. Corresponding authors: Hak Chang, M.D., Ph.D. , Department of Plastic and Reconstructive Surgery,. Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Phone: 82-2-2072-3086, Fax: 82-2-747-5130, E-mail: hchang@snu.ac.kr ©2019American Society of Plastic Surgeons

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