Journal Article Accepted manuscript Human umbilical cord mesenchymal stem cells treated anti-MDA5 antibody-positive dermatomyositis with interstitial lung disease: a case report Get access Runlu Zhou, Runlu Zhou The Second Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Xiao Jin, Xiao Jin The Second Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Juan Li, Juan Li Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Yucong He, Yucong He The Second Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Tianming Gao, Tianming Gao Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Chenghua Zhu, Chenghua Zhu Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Yan Wang, Yan Wang Jiangsu Cell Tech Medical Research Institute, Nanjing, Jiangsu, 211166, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Ganzhu Feng Ganzhu Feng Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Correspondence to Ganzhu Feng, Address: No. 121 Jiangjiayuan Rd, Gulou District, Nanjing 210011, Jiangsu, China, Email: fgz62691@163.com Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, keae285, https://doi.org/10.1093/rheumatology/keae285 Published: 22 May 2024 Article history Received: 09 October 2023 Revision received: 27 March 2024 Accepted: 25 April 2024 Published: 22 May 2024

Previously, we demonstrated the therapeutic effects of human umbilical cord mesenchymal stromal cells (hUC-MSCs) in severe coronavirus disease 2019 (COVID-19) patients. In this 3-month follow-up study, we examined discharged patients who had received hUC-MSC therapy to assess the safety of this therapy and the health-related quality of life (HRQL) of these patients. The follow-up cohort consisted of 28 discharged severe COVID-19 patients who received either the standard treatment (the control group) or the standard treatment plus hUC-MSC therapy. We examined liver function, kidney function, pulmonary function, coagulation, tumor markers, and vision. We also conducted electrocardiography (ECG) analysis, let the patients answer the St. George's Respiratory Questionnaire (SGRQ), and performed computed tomography (CT) imaging for assessing the lung changes. No obvious adverse effects were observed in the hUC-MSC group after 3 months. Measurements of blood routine index, C-reactive protein and procalcitonin, liver and kidney function, coagulation, ECG, tumor markers, and vision were almost within the normal ranges in both the treatment and control groups. Forced expiratory volumes in 1 s (FEV1) (% of predicted) were 71.88% +/- 8.46% and 59.45% +/- 27.45% in the hUC-MSC and control groups (P < 0.01), respectively, and FEV1/forced vital capacity (FEV1/FVC) ratios were 79.95% +/- 8.00% and 58.97% +/- 19.16% in the hUC-MSC and control groups, respectively (P < 0.05). SGRQ scores were lower in the hUC-MSC group than in the control group (15.25 +/- 3.69 vs. 31.9 +/- 8.78, P < 0.05). The rate of wheezing in the hUC-MSC group was also significantly lower than that in the control group (37.5% vs. 75%, P < 0.05). There were no significant differences in CT scores between the two groups (0.60 +/- 0.88 vs. 1.00 +/- 1.31, P = 0.917). Overall, the intravenous transplantation of hUC-MSCs accelerated partial pulmonary function recovery and improved HRQL, indicating relative safety and preliminary efficacy of this treatment for patients with severe COVID-19.

Our study investigates the effect of high expression of Sirt2 in MSCs (MSCs-Sirt2) on Her-2 breast cancer cell proliferation. A mouse subcutaneous xenograft tumor model was established and MSCssirt2 analysis was performed on nude mice. TUNEL staining, flow cytometry, western-blot, real-time PCR and immunohistochemistry were used to detect cancer cell apoptosis. The number of NK cells infiltrated by flow cytometry detected the tumor tissue of tumor-bearing mice, and its killing activity on tumor-bearing mice was detected by isotope labeling and release method. The levels of TNF-α, IFN-γ, IL-8, IL-6 and IL-10 were detected by ELISA. Caspase-3 level was decreased in the MSCs group ( P <0.01) while increased in the MSCs-sirt2 group ( P <0.001). However, PCNA expression showed an opposite profile in the Her-2 group and MSCs-sirt2 group compared to Caspase-3 level ( P <0.01). The tumor volume and weight in the MSCs-sirt2 group was significantly reduced ( P < 0.01), while increased in the MSCs group significantly ( P < 0.05). The number of Ki-67-positive tumor cells in MSCs-sirt2 group was significantly reduced ( P <0.01) and increased in MSCs group ( P < 0.001) with oppositive number of TUNEL-positive tumor cells in the MSCs-sirt2 group and MSCs group ( P <0.01). IFN-γ level showed an upward trend ( P <0.001). The NK cell toxicity of MSCs-Sirt2 group was significantly higher ( P <0.001). MSCs-Sirt2 has an inhibitory effect on Her-2 breast cancer cell growth by enhancing the local inflammatory response of NK cells.

Background: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. Objectives: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. Methods: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. Measurements and Main Results: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34% . In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. Conclusions: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19.