Repopulating Kupffer cells originate directly from hematopoietic stem cells.

BACKGROUND: Kupffer cells (KCs) originate from yolk-sac progenitors before birth. Throughout adulthood, they self-maintain independently from the input of circulating monocytes (MOs) at a steady state and are replenished within 2 weeks after having been depleted, but the origin of repopulating KCs in adults remains unclear. The current paradigm dictates that repopulating KCs originate from preexisting KCs or monocytes, but there remains a lack of fate-mapping evidence. METHODS: We first traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate-mapping mouse models, respectively. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC-depletion in mice. Finally, we traced the fate of hematopoietic stem cells (HSCs) in an HSC-specific fate-mapping mouse model, in the context of chronic liver inflammation induced by repeated carbon tetrachloride treatment. RESULTS: By using fate-mapping mouse models, we found no evidence that repopulating KCs originate from preexisting KCs or MOs and found that in response to KC-depletion, HSCs proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Then, in the chronic liver inflammation context, we confirmed that repopulating KCs originated directly from HSCs. CONCLUSION: Taken together, these findings provided in vivo fate-mapping evidence that repopulating KCs originate directly from HSCs, which presents a completely novel understanding of the cellular origin of repopulating KCs and shedding light on the divergent roles of KCs in liver homeostasis and diseases.

Efficacy and safety of retention enema with traditional Chinese medicine for ulcerative colitis: A meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy and safety of retention enema with traditional Chinese medicine (TCM) for ulcerative colitis (UC) through a meta-analysis of published studies. METHODS: Literatures were retrieved from five electronic databases. Quality evaluation and meta-analysis were respectively conducted using the Cochrane collaboration and RevMan5.3. Overall quality of evidence was evaluated using GRADE system. Effect sizes were pooled using random effect models. RESULTS: Seventeen RCTs were included. Compared with routine pharmacotherapies (RPs), TCM enema exhibited a statistically significant difference in clinical efficacy and reduction of the recurrence rate. The results of qualitative description for other endpoints, such as improvements in anabrosis, ulcer, diarrhea, and hematochezia, suggested that TCM enema had better efficacy than RPs. Furthermore, the incidence of side effects in TCM was lower than that in RPs. CONCLUSION: This meta-analysis confirmed the efficacy and safety of TCM enema for improving UC symptoms. However, further well-designed researches are needed.