Paris Cardiovascular Research Center

Vascularized composite allotransplantation (VCA) has transformed reconstructive surgery for patients with severe tissue defects. Nonetheless, donor shortages remain a major limitation. Cross-sex VCA (CS-VCA) has been proposed as a means of expanding the donor pool, but concerns persist regarding potentially heightened rejection risks in sex-mismatched transplants. This review examines published adult CS-VCA cases up to May 2025. The primary outcomes analyzed were acute rejection episodes, allograft survival, immunological complications, and sequelae affecting form and function. Nine CS-VCA cases were identified (six upper extremity, one lower extremity, and two abdominal wall transplants). Eight involved female donors (median age, 47 years) and male recipients (median age, 30 years). Acute rejection occurred in five of nine cases; however, 11 of 13 allografts remained viable at follow-up (6-41 months) under immunosuppressive therapy. Two cases developed vascular complications, resulting in technical failure and partial amputation, respectively. Higher human leukocyte antigen (HLA) mismatches (mean, 5) were associated with complications, while fewer mismatches (mean, 3) correlated with better outcomes. In contrast to trends in solid organ transplantation, female-to-male CS-VCA demonstrated relatively favorable outcomes in the limited cases reported. These findings suggest that CS-VCA may be a feasible strategy to expand the VCA donor pool, provided that patient selection is careful, ABO/Rh and HLA compatibility are prioritized, and rigorous immunological monitoring is maintained. Further studies should investigate sex-specific immune mechanisms to optimize long-term success rates.

Beyond cardiac impairment, myocardial infarction (MI) affects the central nervous system (CNS), where it has been associated with neuroinflammation and cognitive dysfunction. Microglia, the resident immune cells of the CNS, are key regulators of neuroinflammatory processes. However, the transcriptional landscape of microglia following MI remains incompletely understood. We hypothesized that MI induces transcriptional remodeling in microglia that may reflect altered metabolic regulation. Male C57BL/6J mice underwent permanent LAD ligation or sham surgery. Five days post-MI, CD45-intermediate and SiglecH/CD11b-positive immune cells were isolated from cortical and subcortical regions by FACS and subjected to single-cell RNA sequencing. Complementary exploratory metabolic assays included assessment of mitochondrial mass and membrane potential as well as glucose uptake. Microglia represented the predominant immune cell population in both the cortex and subcortex. Subclustering revealed a significantly increased proportion of a "low translational" microglial subset after MI. Pseudobulk differential expression and gene set enrichment analyses demonstrated significant downregulation of translation-related pathways in cortical microglia and proteostasis-associated pathways in subcortical microglia. These transcriptional changes were accompanied by a significant reduction in mitochondrial mass and metabolic observations consistent with altered energetic regulation, although several functional readouts did not reach statistical significance. Experimental MI is associated with region-specific transcriptional remodeling of microglia, characterized by reduced expression of energy-intensive and proteostasis-related pathways. Exploratory metabolic observations are consistent with altered energetic regulation but require confirmation in adequately powered studies. These findings suggest that systemic cardiac injury is linked to microglial transcriptional adaptation in the early post-infarction phase.

Some pediatric tracheal pathologies remain therapeutic dead ends for which current palliative strategies are fraught with serious complications. With the aim of a tracheal replacement, our team has previously developed and patented a clinical grade partially decellularized trachea (PDT) from porcine tracheas. The aim of this work was to study and compare the biointegration mechanisms of this PDT in vivo, in a pig cervical muscle, with or without immunosuppressant. The secondary objective was to evaluate the optimal maturation time of the PDT in this heterotopic position. In total, 11 female Large White/Landrace pigs, weighing between 50 and 70 kg were included in this study. The mean age of the animals at the implantation was 4.8 months. The PDTs were implanted in a cervical muscle of pigs for either 28 days, with or without cyclosporin A treatment, or for 56 days without immunosuppression. Histological evaluation showed very good PDT biointegration, characterized by neovascularization and fibroblast colonization, and no detectabale infection. Additionally, tissue and blood analyses showed no signs of graft rejection or surrounding tissue necrosis. Immunosuppression did not show any superiority in terms of biointegration after 28 days of treatment. After 56 days of implantation, a more significant degradation of the cartilage. Therefore, the optimal condition for PDT maturation proved to be 28 days, without immunosuppression.