Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial

Abstract

Background: Mesenchymal stem cells (MSCs) are known to have immunomodulatory, anti-inflammatory, anti-apoptotic, and angiogenesis effects that are useful for relieving inflammation, recovery, and protection of lung tissues in COVID-19 patients. Secretome, a secretory product of MSCs, has several advantages over MSCs. We conducted a study to investigate secretomes’ effectiveness and safety profile as a treatment for severe COVID-19. Methods: A double-blind, multicenter, randomized, placebo-controlled trial was conducted between February 2021 and July 2021 in three top COVID-19 referral hospitals in the Greater Jakarta area, Indonesia. Eligible subjects (n=40) were randomized in a 1:1 ratio to an intervention group (n=20) and a control group (n=20). The primary outcome of this study was the changes in inflammatory markers and the ratio of inflammatory to anti-inflammatory markers. The secondary outcomes of this study included clinical outcome, laboratory outcome, radiological outcome, RT-PCR result conversion, and safety profile of MSC secretome. Results: Our analysis showed that on the 14th day after placebo administration, IL-6 level in the control group was significantly increased [4.110 (2.403–12.820) at baseline to 13.320 (2.958–33.285) on the 14th day after intervention, p=0.017]. The IL-6/IL-10 ratio in the control group was significantly increased (p=0.036) on the 14th day after placebo administration. We also found that most of the subjects who received placebo had high levels of IL-6 and ferritin (p=0.043) on the seventh day after the intervention. However, we found no significant differences in inflammatory marker levels on the seventh day and 14th day after intervention between both groups. There was no adverse event reported. There were no significant differences in the laboratory outcome, radiology outcome, RT-PCR result conversion, and safety profiles between both groups. Conclusions: MSC secretome can control inflammation in patients with severe COVID-19 and has a good safety profile. MSC secretome is a promising treatment modality for severe COVID-19.

Effectiveness of RCTs Pooling Evidence on Mesenchymal Stem Cell (MSC) Therapeutic Applications During COVID-19 Epidemic: A Systematic Review

“…The study overall records (12,567) are extracted from various databases (Scopus, Web of Science, PUBMED, EMBASE, Science Direct, Cochrane Library, and Google Scholar), and 14 RCTs were included in this SR, 1 , 58 , 83 , 86 , 88 , 93 , 106–113 whereas remaining records were excluded with various reasons and are explained in Figure 1 in detailed. The CASP checklist criteria were considered for inclusion of the studies and considered as high-quality studies (CASP check attached as Supplementary File 1 ).…”

“… Infusion of UC-MSCs is safe and can play a significant role as adjuvant therapy, both in the early phases, averting severe consequences, and in the chronic phase. Ayca Sultan Sahin 106 2022 Turkey Prospective randomized single-center clinical trial May to July 2020 Health science university, Ka nuni sultan Suleyman education and training hospital, department of anesthesiology and reani mation in Istanbul COVID-19 patients 21 COVID-19 patients Patients were detached into 3 groups: those who were intubated without comorbidities (n=7), those who were intubated with comorbidities (n=7), and those who were not intubated (n=7). Patients were detached into 3 groups: those who were intubated without comorbidities (n=7), those who were intubated with comorbidities (n=7), and those who were not intubated (n=7).…”

Two New Potential Therapeutic Approaches in Radiation Cystitis Derived from Mesenchymal Stem Cells: Extracellular Vesicles and Conditioned Medium

“…As of today, MSC-EVs and MSC-CM are being evaluated in phase I/II clinical trials for the prevention or management of severe forms of COVID-19, and also inflammatory digestive pathologies, for their anti-inflammatory properties [ 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. This confirms the feasibility of these new therapeutic possibilities in clinical practice, with intravenous but also intranasal delivery.…”

Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial

“…Underlying data OSF: "Effectiveness and Safety Profile of Mesenchymal Stem Cell Secretomes as a Treatment for Severe Cases of COVID-19", https://doi.org/10.17605/OSF.IO/NUAVY. 28 This project contains the following file:…”

“…• Study Raw Data.xlsx Reporting guidelines OSF: CONSORT checklist for 'Effectiveness and safety profile of mesenchymal stem cell secretomes as a treatment for severe cases of COVID-19: a randomized controlled trial', https://doi.org/10.17605/OSF.IO/NUAVY. 28 Data are available under the licence of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).…”