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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 x 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.)
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Objective To investigate the renoprotective effects of autologous transplantation of adipose-derived mesenchymal stem cells (ADMSCs) in diabetic rats. Methods Sprague-Dawley (SD) rats were injected intraperitoneally with 40 mg/kg streptozotocin (STZ) for 5 consecutive days to induce type 1 diabetes. Four weeks following STZ injection, eighteen SD rats were randomized into two groups: the diabetic group (n = 9) and the ADMSCs group (n = 9). Normal nondiaetic rats were set as the normal control (n = 9). Autologous ADMSCs were cultured and identified in vitro , which were intravenously injection to the ADMSCs group rats via the tail vein. At 8 weeks after transplantation, levels of blood glucose, insulin, serum urea nitrogen, serumcreatinine and urine protein were measured. Meanwhile the body weight and kidney weight were examined. Results Mesenchymal cell surface markers were expressed in the cultured ADMSCs. The ADMSCs could differentiate into the adipogenic and osteoblastic lineages. Both the diabetic group and the ADMSCs group rats had higher levels of blood glucose , urea nitrogen , serum creatinine , urine protein and higher ratio of the kidney weight/body weight than those in the normal control group (P < 0.05, respectively). Blood glucose, urea nitrogen and the ratio of kidney weight/body weight in the ADMSCs group rats were significantly decreased compared with the diabetic group (P < 0.05, respectively). The decreased insulin level was attenuated after transplantation of ADMSCs (P < 0.05). Besides, levels of serum creatinine and urine protein in the ADMSCs group were lower than those in the diabetic group with no significant difference. Conclusion Autologous transplantation of ADMSCs can improve metabolic disorder and relieves diabetic renal damage.
