External Volume Expansion Up-Regulates CXCL12 Expression and Enhances Mesenchymal Stromal Cell Recruitment toward Expanded Prefabricated Adipose Tissue in Rats

Background: External volume expansion devices are effective for adipose tissue regeneration. However, the detailed mechanisms by which external volume expansion devices induce adipose tissue regeneration remain unclear. Methods: An external volume expansion device was used to construct expanded prefabricated adipose tissue in a rat model. CXCL12 levels in local exudate and serum were measured by enzyme-linked immunosorbent assay, and CXCL12 expression in adipose tissue was assessed immunohistochemically. Fluorescent dye (CM-DiI)-labeled bone marrow-derived mesenchymal stromal cells and labeled mesenchymal stromal cells 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 external volume expansion device application. CXCL12(+) cell counts were significantly higher in the external volume expansion than in the control group. These CXCL12(+) cells were mainly columnar or cuboidal and began to express peroxisome proliferator-activated receptor on day 9. CM-DiI-labeled mesenchymal stromal cells were successfully recruited to the expanded prefabricated adipose tissue, a process partly inhibited by the CXCR4 antagonist AMD3100. These recruited CM-DiI-labeled mesenchymal stromal cells were found among the CXCL12(+) columnar cells. Conclusions: External volume expansion devices enhance CXCL12 expression levels, especially in columnar and cuboidal cells. The CXCL12/CXCR4 pathway is involved in recruiting circulating mesenchymal stromal cells to participate in adipose regeneration. These findings may reveal the mechanism underlying external volume expansion and provide insights into the refinement of these devices.