Evaluation of the safety and efficacy of using human menstrual blood‐derived mesenchymal stromal cells in treating severe and critically ill COVID‐19 patients: An exploratory clinical trial

Abstract

The coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified in December 2019 and has subsequently spread worldwide. Currently, there is no effective method to cure COVID‐19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID‐19, especially for severe and critical patients. Menstrual blood‐derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty‐four patients were enrolled from January to April 2020 in a multicenter, open‐label, nonrandomized, parallel‐controlled exploratory trial. Twenty‐six patients received allogeneic, menstrual blood‐derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 10 7 MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1‐month period following MSC infusion. Safety was measured using the frequency of treatment‐related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group; P = .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO 2 was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC‐based therapy may serve as a promising alternative method for treating severe and critical COVID‐19.

The safety and efficacy of mesenchymal stem cells in the treatment of COVID-19-associated pneumonia: a systematic review and meta-analysis

“…Abstract and full-text screening identified 22 studies with 371 patients to be included for the data extraction. All included studies were assessed as good [10,12,[22][23][24][25][26]32,35,36,38,39] or fair [13,[27][28][29][30][31]33,34,37,40] according to the NHLBI quality assessment tool (Table S2).…”

“…Culture-expanded allogeneic MSCs were used in all 22 included studies. Allogeneic umbilical cordderived MSCs were used in studies [22][23][24][25][26]29,30,32,34,[36][37][38][39], Wharton's jelly-derived MSCs in three studies [12,33,40], menstrual blood-or adipose tissue-or placenta-derived MSCs were separately used in one study [10,28,35]. Four studies did not report the tissue origin of the MSCs [13,27,31,37](Table 3).…”

“…Eleven studies reported on baseline oxygenation indicators of patients [10,13,26,27,29,30,32,35,37,38,40]. General symptoms such as fever, cough, and dyspnea were reported in 16 studies [10,12,13,23,24,27,29,[32][33][34][35][36][37][38][39][40], and lung imaging evaluation showed COVID-19 related pneumonia in 15 studies [10,12,23,25,27,29,[32][33][34][35][36][37][38][39][40].…”

“…The disease severity of the patient's condition was Critical (n = 63), Severe (n = 260), and Moderate (n = 10) in 19 studies [10,12,13,[22][23][24][25][27][28][29][30][31][32][33][34]36,[38][39][40]; and the patients in one study were divided into "Mild-to-moderate" (n = 6) and "Moderate-to-severe" (n = 18) according to the severity of ARDS [26]. The average age of study participants was 45.1 to 61.0 years for MSCs group and 39.0 to 65.0 years for control group in the comparative studies [13,[22][23][24][25][26][27]. In the comparative studies, the disease severity of MSCs group were Critical (n = 13), Severe (n = 115), and Moderate (n = 8), and those of control group were Critical (n = 11), Severe (n = 105), and Moderate (n = 8) [13,[22][23][24][25][26][27].…”

“…The average age of study participants was 45.1 to 61.0 years for MSCs group and 39.0 to 65.0 years for control group in the comparative studies [13,[22][23][24][25][26][27]. In the comparative studies, the disease severity of MSCs group were Critical (n = 13), Severe (n = 115), and Moderate (n = 8), and those of control group were Critical (n = 11), Severe (n = 105), and Moderate (n = 8) [13,[22][23][24][25][26][27].…”