Background: Mesenchymal stem cell (MSC) therapy has been shown to be a promising option for liver fibrosis treatment. However, critical factors affecting the efficacy of MSC therapy for liver fibrosis remain unknown. Follistatin-like 1 (FSTL1), a TGF-β-induced matricellular protein, is documented as an intrinsic regulator of proliferation and differentiation in MSCs. In the present study, we characterized the potential role of FSTL1 in MSC-based anti-fibrotic therapy and further elucidated the mechanisms underlying its action. Methods: Human umbilical cord-derived MSCs were characterized by flow cytometry. FSTL1^low MSCs were achieved by FSTL1 siRNA. Migration capacity was evaluated by wound-healing and transwell assay. A murine liver fibrotic model was created by carbon tetrachloride (CCl₄) injection, while control MSCs or FSTL1^low MSC were transplanted via intravenous injection 12 weeks post CCl₄ injection. Histopathology, liver function, fibrosis degree, and inflammation were analysed thereafter. Inflammatory cell infiltration was evaluated by flow cytometry after hepatic nonparenchymal cell isolation. An MSC-macrophage co-culture system was constructed to further confirm the role of FSTL1 in the immunosuppressive capacity of MSCs. RNA sequencing was used to screen target genes of FSTL1. Results: FSTL1^low MSCs had comparable gene expression for surface markers to wildtype but limited differentiation and migration capacity. FSTL1^low MSCs failed to alleviate CCl₄-induced hepatic fibrosis in a mouse model. Our data indicated that FSTL1 is essential for the immunosuppressive action of MSCs on inflammatory macrophages during liver fibrotic therapy. FSTL1 silencing attenuated this capacity by inhibiting the downstream JAK/STAT1/IDO pathway. Conclusions: Our data suggest that FSTL1 facilitates the immunosuppression of MSCs on macrophages and that guarantee the anti-fibrotic effect of MSCs in liver fibrosis.

Acute myeloid leukemia (AML) is a deadly heterogeneous hematologic malignancy. Despite the well-characterized genetic characteristics and new promising targeted therapies for AML, the clinical outcome remains suboptimal. Galectin-9 (Gal-9) is a good potential target due to its immunosuppressive capacity in inflammatory processes. In our study, we firstly performed a wide range of integrated bioinformatical approach to assess the importance of Gal-9 by analyzing the expression, potential function and prognostic impact in AML. The results indicated that Gal-9 is overexpressed in AML cells, especially when relapse after hematopoietic stem cell transplantation (HSCT) and predicts poor prognosis. Co-expression analysis showed Gal-9 has a strong positive correlation with proteasome subunit beta type-8 (PSMB8), which was also highly expressed in AML with poor prognosis, implying a synergy in cell survival, cell signaling and the development of AML. In summary, we have confirmed the overexpression of Gal-9 and its partner PSMB8 in AML and validated their importance as prognostic factors. We propose that Gal-9 and PSMB8 could be a promising molecular target for treatment of AML and may provide more combined treatment options, especially in patients with relapse after HSCT.

Acute myeloid leukemia (AML) encompasses a clinically and genetically diverse set of blood cancers caused by abnormally rapid expansion of myeloid progenitor cells in the bone marrow and extramedul...

Adult stem cell therapy holds great promise for treating decompensated liver cirrhosis on the basis of animal studies, despite uncertainty about its clinical therapeutic efficacy and unclear underlying mechanisms. Here, we investigated the role of follistatin-like 1 (FSTL1), a profibrotic and proinflammatory matricellular protein, in inflammation-related heterogeneity in stem cell therapy. Our results showed that a high level of circulating FSTL1 is significantly correlated with therapeutic response in patients with cirrhosis. FSTL1 facilitated MSC-mediated early recruitment of Ly6C⁺ inflammatory macrophages within 24 h postinfusion, which was essential for the empowerment of MSCs and subsequent Ly6C⁻CX3CR1⁺ macrophage remodelling at 48 h postinfusion. Fstl1 deficiency abrogated early macrophage recruitment and effective Ly6C⁻CX3CR1⁺ macrophage accumulation, resulting in the poor antifibrotic effect of MSCs in mice. Whereas, recombinant FSTL1 protein restored the therapeutic efficacy of MSCs in CCl₄-injured Fstl1 ^+/− mice. Mechanistically, host FSTL1 enhanced rapid recycling of CCR2 to the membrane via activation of the CD14/TLR4/NF-κB/ATP6V1G2 axis, leading to early recruitment of Ly6C⁺ monocytes /macrophages. Taken together, our findings revealed that FSTL1 is a critical regulator of the fibrotic immune microenvironment and facilitates subsequent stem cell therapy. These data suggest that FSTL1 could serve as a predictive biomarker of stem cell therapy response in patients with liver cirrhosis.

Background: Acute myeloid leukemia (AML) patients with a Fms‐like tyrosine kinase 3 (FLT3) mutation have a high incidence of relapse despite allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and a subsequent poor prognosis. FLT3 inhibitors (FLT3i) have been suggested to reduce the post‐transplant relapse risk in recent studies. As more evidence is accumulated, we perform the present meta‐analysis to assess the efficacy and safety of FLT3i as post‐transplant maintenance therapy in AML patients.Methods: Literature search was performed in public databases from inception to December 31, 2021. Overall survival (OS), relapse‐free survival (RFS), cumulative incidence of relapse (CIR), non‐relapse mortality (NRM), graft‐versus‐host disease (GVHD) and adverse events were compared between FLT3i and control groups. Pooled hazard ratio (HR) or relative risk (RR) with corresponding 95% confidence interval (CI) were calculated.Results: We identified 12 eligible studies with 2282 FLT3‐mutated AML patients who had received HSCT. There was no between‐study heterogeneity and a fix‐effect model was used. Post‐transplant FLT3i maintenance significantly prolonged OS (HR = 0.41, 95%CI: 0.32–0.52, p < 0.001) and RFS (HR = 0.39, 95%CI 0.31–0.50, p < 0.001), and reduced CIR (HR = 0.31, 95%CI 0.20–0.46, p < 0.001) as compared with control. There were no significant risk differences in NRM (RR = 0.69, 95%CI 0.41–1.17, p = 0.169), acute GVHD (RR = 1.17, 95%CI 0.93–1.47, p = 0.175), chronic GVHD (RR = 1.31, 95%CI 0.91–1.39, p = 0.276) and grade ≥3 adverse events between both groups, except for skin toxicity (RR = 5.86, 95%CI 1.34–25.57, p = 0.019).Conclusion: Post‐transplant FLT3i maintenance can improve survival and reduce relapse in FLT3‐mutated AML patients and is tolerable.