External volume expansion up-regulates CXCL12 expression and enhances mesenchymal stromal cell recruitment toward expanded prefabricated adipose tissue in rats

Background: External volume expansion (EVE) devices are effective for adipose tissue regeneration. However, the detailed mechanisms by which EVE devices induce adipose tissue regeneration remain unclear. Methods: An EVE device was used to construct expanded prefabricated adipose tissue (EPAT) in a rat model. CXCL12 levels in local exudate and serum were measured by ELISA, and CXCL12 expression in adipose tissue was assessed immunohistochemically. Fluorescent dye (CM-DiI) labeled bone marrow-derived mesenchymal stromal cells (MSCs) and labeled MSCs pretreated with the CXCR4 antagonist AMD3100 were transplanted into rats and tracked in vivo by fluorescence imaging. Results: CXCL12 levels in local exudate and serum peaked 2 and 7 days, respectively, after EVE device application. CXCL12+ cell counts were significantly higher in the EVE than in the control group. These CXCL12+ cells were mainly columnar or cuboidal and began to express peroxisome proliferator-activated receptor γ (PPARγ) on day 9. CM-DiI labeled MSCs were successfully recruited to the EPAT, a process partly inhibited by the CXCR4 antagonist AMD3100. These recruited CM-DiI labeled MSCs were found among the CXCL12+ columnar cells. Conclusion: EVE devices enhance CXCL12 expression levels, especially in columnar and cuboidal cells. The CXCL12-CXCR4 pathway is involved in recruiting circulating MSCs to participate in adipose regeneration. These findings may reveal the mechanism underlying EVE and provide insights into the refinement of these devices. Financial Disclosure: This work was supported by National Nature Science Foundation of China (81471881, 81601702, 81671931), Natural Science Foundation of Guangdong Province of China (2014A030310155), Administrator Foundation of Nanfang Hospital (2014B009, 2015Z002, 2016Z010, 2016B001). Corresponding Author: Dr Jianhua Gao, Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong 510515, P. R. China., Phone/fax: +86 (020) 62787550, Gaopsnf@163.com Dr. Ziqing Dong, Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong 510515, P. R. China. Phone/fax: +86 (020) 61641869, doctordongziqing@hotmail.com ©2017American Society of Plastic Surgeons