Meta-Analysis of Porcine Beige Adipogenesis with Cross-Species CD137-CD137L Molecular Docking: Potential Implications for Pig-to-Human Xenotransplantation

Abstract

Breakthroughs in gene-editing technologies have brought pig-to-human xenotransplantation to the clinical forefront. Nevertheless, the micro-scale impacts of the complex pathophysiological milieu within recipients on grafts have long been overlooked by the academic community. Focusing on stromal vascular fraction (SVF) cells and preadipocytes widely present in donor organs, this study explores the potential mechanism underlying beige adipogenesis induced by post-operative anti-inflammatory drugs (e.g., dexamethasone) and surgical stress (norepinephrine), as well as its possible relationship with host immune system activation. The literature search and study-selection reporting were informed by PRISMA 2020. Five information sources were searched, and nine relevant studies on experimentally induced porcine adipose beiging, predominantly in vitro, were included in marker-specific meta-analyses. The meta-analysis showed a higher pooled expression of CD137, CIDEA, UCP3, PGC1α and DIO2 during experimentally induced porcine beige adipogenesis. To explore the structural plausibility of cross-species interaction, molecular docking analysis of the candidate protein CD137 was performed using AlphaFold 3. The predicted binding energies were −9.4 kcal/mol for porcine CD137–human CD137L and −9.0 kcal/mol for the human homologous complex. These computational predictions suggest a structurally plausible interaction, but the results do not demonstrate stronger biological binding, macrophage activation, or immune rejection. Overall, the findings support a hypothesis that porcine adipocyte beiging and CD137-related cross-species interactions may be relevant to xenograft immunometabolism; direct experimental validation in xenotransplantation models is required.