Xenogenic induction of adipose tissue and maintenance through pre- and post-conditioning using external volume expansion

Abstract

Abstract External volume expansion (EVE) has been shown to improve fat graft survival. In this study, we investigated the xenogenic implantation of human allograft adipose matrix (AAM) in non-immunocompromised mice in combination with pre- and post-conditioning with EVE to assess long-term adipose tissue survival. Sixty-eight recipient sites in thirty-four eight-week-old wild type (C57BL/6J) mice were separated into four groups. Thirty-four sites received no conditioning and either a subcutaneous injection of 300 μl saline (n = 17; PBS group) or AAM (n = 17; AAM group). Thirty-four sites received pre-conditioning with EVE (Day -7–3 pre-grafting) and 300 μl of AAM. Seventeen of these sites received immediate post-conditioning (Day 1–5 post-grafting) and 17 delayed post-conditioning (Day 28–32 post-grafting). Tissue was harvested at week 12 for analysis. At 12 weeks, immediate and delayed post-conditioning enabled higher volume retention (p = 0.02 and p < 0.0001, respectively). Adipose Stem Cells were greater in the AAM+Del-EVE group compared to the AAM (p = 0.01). Microvessel density was lower in the AAM group compared to the AAM+Imm-EVE (p = 0.04) and AAM+Del-EVE group (p = 0.02). Macrophage infiltration was lower in the AAM+Imm-EVE (p = 0.002) and AAM+Del-EVE (p = 0.003) groups compared to the AAM group. PCR analysis and Western blotting identified a significantly higher expression of PPAR-γ, LPL and VEGF with delayed-conditioning. Pre- and post-conditioning, particularly delayed-post-conditioning, of the recipient site optimized the microenvironment allowing significant adipogenesis and survival of neo-adipose tissue through robust angiogenesis. This study supports that xenogenic transplantation of adipose matrix allows adipose tissue formation and survival with EVE as an adjuvant.