%0 Journal Article
%T Kupffer cells abrogate homing and repopulation of allogeneic hepatic progenitors in injured liver site.
%A Abbas N
%A You K
%A Getachew A
%A Wu F
%A Hussain M
%A Huang X
%A Chen Y
%A Pan T
%A Li Y
%J Stem Cell Res Ther
%V 15
%N 1
%D 2024 Feb 20
%M 38378583
%F 8.079
%R 10.1186/s13287-024-03656-w
%X <B>BACKGROUND: </B>Allogeneic hepatocyte transplantation is an emerging approach to treat acute liver defects. However, durable engraftment of the transplanted cells remains a daunting task, as they are actively cleared by the recipient's immune system. Therefore, a detailed understanding of the innate or adaptive immune cells-derived responses against allogeneic transplanted hepatic cells is the key to rationalize cell-based therapies.<BR><B>METHODS: </B>Here, we induced an acute inflammatory regenerative niche (3-96 h) on the surface of the liver by the application of cryo-injury (CI) to systematically evaluate the innate immune response against transplanted allogeneic hepatic progenitors in a sustained micro-inflammatory environment.<BR><B>RESULTS: </B>The resulting data highlighted that the injured site was significantly repopulated by alternating numbers of innate immune cells, including neutrophils, monocytes and Kupffer cells (KCs), from 3 to 96 h. The transplanted allo-HPs, engrafted 6 h post-injury, were collectively eliminated by the innate immune response within 24 h of transplantation. Selective depletion of the KCs demonstrated a delayed recruitment of monocytes from day 2 to day 6. In addition, the intrasplenic engraftment of the hepatic progenitors 54 h post-transplantation was dismantled by KCs, while a time-dependent better survival and translocation of the transplanted cells into the injured site could be observed in samples devoid of KCs.<BR><B>CONCLUSIONS: </B>Overall, this study provides evidence that KCs ablation enables a better survival and integration of allo-HPs in a sustained liver inflammatory environment, having implications for rationalizing the cell-based therapeutic interventions against liver defects.