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Background Mesenchymal stem cells (MSCs) therapy has great potential for Alzheimer’s disease (AD) treatment. Here, we investigated the roles of BMSCs-exosomes containing growth differentiation factor-15 (GDF-15) in regulating SH-SY5Y cell injury in AD. Methods The SH-SY5Y cell injury model was constructed by treating SH-SY5Y cells with 10 μM Aβ42. GDF-15 expression was assessed using qRT-PCR and western blot. CCK8 assay and flow cytometry assay were employed to elevate cell proliferation and apoptosis, respectively. The expression levels of inflammatory factors (IL-6, IL-1β, TNFα and IL-8) and Aβ42 were detected using ELISA. Besides, the levels of apoptosis-related proteins and AKT pathway-related proteins were determined using western blot. Results Our results displayed that BMSCs-EVs treatment elevated cell viability, while suppressed cell apoptosis and inflammation in Aβ42-treated SH-SY5Y cells. Exosomes secreted by BMSCs after GDF-15 silence lost the ability to restore Aβ42-induced SH-SY5Y cell damage. GDF-15 treatment restored Aβ42-induced SH-SY5Y cell damage, while it was eliminated by AKT pathway inhibition. BMSCs-exosomes containing GDF-15 upregulated NEP and IDE via activation of AKT/GSK-3β/β-catenin pathway, thereby degrading Aβ42 protein to relieve SH-SY5Y cell damage. Conclusion BMSCs-exosomes containing GDF-15 alleviated SH-SY5Y cell damage via AKT/GSK-3β/β-catenin. Our work confers a promising therapeutic strategy for AD.

Chronic liver diseases have become a significant health issue worldwide and urgently require the development of novel therapeutic approaches, in addition to liver transplantation. Recent clinical and preclinical studies have shown that cell-based therapeutic strategies may contribute to the improvement of chronic liver diseases and offer new therapeutic options to restore liver function through their roles in tissue impairment and immunomodulation. In this review, we summarize the current progress and analyze the challenges for different types of cell therapies used in the treatment of chronic liver diseases currently explored in clinical trials and preclinical studies in animal models. We also discuss some critical issues regarding the use of mesenchymal stem cells (MSCs, the most extensive cell source of stem cells), including therapeutic dosage, transfusion routine, and pharmacokinetics/pharmacodynamics (PK/PD) of transfused MSCs.

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was −13.31%, 95% CI −29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: −15.45%; 95% CI −30.82%, −0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

BACKGROUNDTreatment of severe Corona Virus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data.METHODSIn this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test, maximum vital capacity, diffusing capacity, and adverse events were recorded and analysed.RESULTS100 COVID-19 patients were finally recruited to receive either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95%CI -29.14%, 2.13%, P=0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P=0.043). The 6-minute walk test showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P=0.057). The incidence of adverse events was similar in the two groups.CONCLUSIONSUC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.)

Background: Treatment of severe Corona Virus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC‑MSCs) to treat patients with severe COVID-19 with lung damage, based on our phase 1 data. Methods: In this randomised, double-blind, and placebo-controlled trial, we recruited 101 eligible patients with severe COVID-19 with lung damage aged between 18–74 years from two hospitals. Enrolled patients were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. We excluded patients with malignant tumours, shock, or other organ failure. The primary endpoint was an altered proportion of whole lung lesion areas from baseline to day 28, measured by chest computed tomography. Other imaging outcomes, 6-minute walk test, maximum vital capacity, diffusing capacity, plasma biomarkers, and adverse events were recorded and analysed. Primary analysis was done in the modified intention-to-treat (mITT) population and safety analysis was done in all patients who started their assigned treatment. Findings: From March 5, 2020, to March 28, 2020, 100 patients were finally enrolled and received either UC-MSCs (n = 65) or placebo (n = 35). During follow-up, the patients receiving UC-MSCs exhibited a trend of numerical improvement in whole lung lesions from baseline to day 28 compared with the placebo cases. UC-MSCs administration significantly reduced the proportions of consolidation lesions from baseline to day 28 in the treated patients compared with the placebo subjects. The 6-minute walk test showed an increased distance in patients treated with UC-MSCs. Notably, UC-MSCs delivery was well tolerated, with no serious adverse events. Interpretation: UC-MSCs treatment is a safe and potentially effective therapeutic approach for patients with severe COVID‑19. The trial suggests that UC-MSCs administration might benefit patients with COVID-19 with lung damage at the convalescent stage as well as the progression stage. Trial Registration: This trial is registered with ClinicalTrials.gov, number NCT04288102. Funding Statement: This trial was supported by The National Key RD The Innovation Groups of the National Natural Science Foundation of China (81721002); The National Science and Technology Major Project (2017YFA0105703). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: Ethical approval was obtained from the institutional review boards of each participating hospital. Written informed consent was obtained from all the enrolled patients or their legal representatives if they were unable to provide consent.