Bone marrow-derived cells repopulate the human peritoneal cavity after allogeneic stem cell transplantation

Abstract In end-stage liver disease, disruption of the gut–liver axis leads to intestinal dysbiosis and impaired barrier function, promoting translocation of bacterial products into the peritoneal cavity and contributing to spontaneous bacterial peritonitis (SBP). The peritoneal cavity harbors a distinct immune landscape dominated by tissue-resident peritoneal macrophages (PMs), which are crucial for pathogen clearance. Severe infections or medical interventions can drastically alter this landscape. While strong evidence from previous studies suggests that PMs originate from infiltrating monocytes, direct experimental proof is still lacking. Here, we studied a patient with allogeneic stem cell transplantation and decompensated cirrhosis. Genetic chimerism enabled tracking of immune cell origin. One year post-transplant, PMs were almost entirely donor-derived yet displayed all features of mature tissue-resident macrophages. A minor fraction of patient-derived small PMs persisted, indicating resilience. Additionally, peritoneal fluid supported macrophage differentiation, underscoring the role of environmental milieu. Our findings provide direct evidence that circulating monocytes can fully replenish PMs.