Internal Expansion Preconditioning of Recipient Site Increases Fat Graft Retention by Enriching Stem Cell Pool and Inducing Browning in Rats

Abstract

In the past four decades, breast cancer incidence rates have risen dramatically, and during 2010 to 2019, the rate increased by 0.5% annually. In 2022, approximately 287,850 new cases of invasive breast cancer will be diagnosed among U.S. women, and 43,250 women will die from breast cancer. 1 In 2018, 63% of patients with stage I or II disease underwent breast-conserving surgery, and 33% underwent mastectomy. 2 Background: Fat grafting has an unsatisfactory retention rate for breast reconstruction because of poor recipient conditions. The contribution of the recipient site to fat grafts is unknown. In this study, the authors hypothesize that tissue expansion could improve fat graft retention by preconditioning the recipient fat pad. Methods: Overexpansion was achieved using 10-mL cylindrical soft-tissue expanders implanted beneath the left inguinal fat flaps of 16 Sprague-Dawley rats (weighing 250 to 300 g), whose contralateral parts were implanted with a silicone sheet as a control. After 7 days of expansion, the implants were removed and both inguinal fat flaps received 1 mL of fat grafts from eight donor rats. Fluorescent dye-labeled mesenchymal stromal cells were injected into rats and tracked in vivo by fluorescence imaging. Transplanted adipose tissue was harvested at 4 and 10 weeks (n = 8 per time point). Results: After 7 days of expansion, OCT4 + (P = 0.0002) and Ki67 + (P = 0.0004) areas were increased with up-regulated expression of CXCL12 in recipient adipose flaps. An increasing number of CM-DiI-positive mesenchymal stromal cells were observed in the expanded fat pad. At 10 weeks after fat grafting, retention rate, measured using the Archimedes principle, was much higher in the expanded group than in the nonexpanded group (0.3019 ± 0.0680 versus 0.1066 ± 0.0402; P = 0.0005). Histologic and transcriptional analyses revealed that angiogenesis was enhanced, and macrophage infiltration was decreased in the expanded group. Conclusion: Internal expansion preconditioning increased circulating stem cells into the recipient fat pad and contributed to improved fat graft retention.