Adipose-derived mesenchymal stem cells for the prevention of capsular contracture

Abstract: Capsular contracture (CC) is the most common complication associated with implant-based breast surgery, with particularly high risk in patients undergoing alloplastic reconstruction surgery followed by radiation therapy. Revision surgery, the only currently effective treatment, carries a high risk of recurrent CC and secondary complications. This work assessed the prophylactic potential of human adipose-derived mesenchymal stem cells (hAD-MSCs) in a novel animal model of radiation-induced CC. A total of 36 female C57Bl/6 mice were randomly assigned to three groups: (1) IMP (silicone implants only), (2) IMP + RAD (silicone implants and irradiation therapy to promote CC), and (3) IMP + RAD + MSCs (silicone implants, irradiation therapy, and local administration of hAD-MSCs). On day 42 post-implantation, animals were euthanized and capsular tissue was subjected to histological and gene expression analyses. In addition, serum transforming growth factor beta (TGF-β) levels were measured. Targeted radiotherapy induced significant CC. In contrast, on day 42 post-irradiation, the capsular thickness in the IMP + RAD + MSCs group was significantly lower, comparable to that of non-irradiated mice. hAD-MSC treatment also resulted in a significant downregulation of pro-fibrotic and pro-inflammatory genes in the capsular tissue. In this study conducted in a murine model, hAD-MSCs demonstrated significant prophylactic potential in preventing radiation-induced CC. Further research is necessary to investigate the underlying mechanisms and to assess the efficacy and safety of this approach. Key messages: Radiotherapy increased capsular thickness and expression of pro-inflammatory and fibrotic genes. Stem cells restored capsular thickness to levels comparable to non-irradiated mice. Stem cells downregulated both pro-fibrotic and pro-inflammatory genes in capsule tissue. Findings highlight the potential of stem cells in preventing radiation-induced capsular contracture.