{Reference Type}: Journal Article
{Title}: Kupffer cells abrogate homing and repopulation of allogeneic hepatic progenitors in injured liver site.
{Author}: Abbas N;You K;Getachew A;Wu F;Hussain M;Huang X;Chen Y;Pan T;Li Y;
{Journal}: Stem Cell Res Ther
{Volume}: 15
{Issue}: 1
{Year}: 2024 Feb 20
{Factor}: 8.079
{DOI}: 10.1186/s13287-024-03656-w
{Abstract}: <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.