Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial [version 2; peer review: 1 approved, 2 approved with reservations]
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 adv...
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F1000 Research Ltd
2022-07-01
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| Online Access: | https://f1000research.com/articles/11-143/v2 |
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| author | Hary Sakti Muliawan Erlina Burhan Mia Elhidsi Heri Wibowo Triya Damayanti Jeanne Adiwinata Pawitan Isabella Kurnia Liem Ismail Hadisoebroto Dilogo Mira Yulianti Adityo Susilo Irandi Putra Pratomo Raden Rara Diah Handayani Rahyussalim - Murdani Abdullah Cosphiadi Irawan Robert Sinto Dita Aditianingsih |
| author_facet | Hary Sakti Muliawan Erlina Burhan Mia Elhidsi Heri Wibowo Triya Damayanti Jeanne Adiwinata Pawitan Isabella Kurnia Liem Ismail Hadisoebroto Dilogo Mira Yulianti Adityo Susilo Irandi Putra Pratomo Raden Rara Diah Handayani Rahyussalim - Murdani Abdullah Cosphiadi Irawan Robert Sinto Dita Aditianingsih |
| author_sort | Hary Sakti Muliawan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2f6393d2270247aebee8e1286b0eaa0d |
| institution | Kabale University |
| issn | 2046-1402 |
| language | English |
| publishDate | 2022-07-01 |
| publisher | F1000 Research Ltd |
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| spelling | doaj-art-2f6393d2270247aebee8e1286b0eaa0d2025-02-07T01:00:01ZengF1000 Research LtdF1000Research2046-14022022-07-0111122039Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial [version 2; peer review: 1 approved, 2 approved with reservations]Hary Sakti Muliawan0Erlina Burhan1https://orcid.org/0000-0002-8115-8293Mia Elhidsi2https://orcid.org/0000-0002-5005-044XHeri Wibowo3Triya Damayanti4https://orcid.org/0000-0002-3779-4372Jeanne Adiwinata Pawitan5https://orcid.org/0000-0002-6551-5238Isabella Kurnia Liem6Ismail Hadisoebroto Dilogo7https://orcid.org/0000-0002-6202-0918Mira Yulianti8Adityo Susilo9Irandi Putra Pratomo10https://orcid.org/0000-0003-0826-3967Raden Rara Diah Handayani11Rahyussalim -12Murdani Abdullah13https://orcid.org/0000-0002-8801-0283Cosphiadi Irawan14Robert Sinto15Dita Aditianingsih16Department of Department of Cardiology and Vascular Medicine, Universitas Indonesia Hospital, Depok, IndonesiaDepartment of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia - Persahabatan Hospital, Jakarta, 10430, IndonesiaDepartment of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia - Persahabatan Hospital, Jakarta, 10430, IndonesiaIntegrated Laboratory, Faculty of Medicine, University of Indonesia, Jakarta, IndonesiaDepartment of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia - Persahabatan Hospital, Jakarta, 10430, IndonesiaDepartement of Histology, University of Indonesia, Jakarta, IndonesiaStem Cell Medical Technology Integrated Service Unit, Faculty of Medicine, University of Indonesia, Jakarta, 10430, IndonesiaStem Cell Medical Technology Integrated Service Unit, Faculty of Medicine, University of Indonesia, Jakarta, 10430, IndonesiaDivision of Pulmonology, Departement of Internal Medicine, Faculty of Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, IndonesiaDivision of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, University of Indonesia,Cipto Mangunkusumo Hospital, Jakarta, IndonesiaDepartment of Pulmonology and Respiratory Medicine, Universitas Indonesia Hospital, Jakarta, IndonesiaDepartment of Pulmonology and Respiratory Medicine, Universitas Indonesia Hospital, Jakarta, IndonesiaDepartment of Orthopaedic and Traumatology, Faculty of Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, 10430, IndonesiaDivision of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, 10430, IndonesiaDivision of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, 10430, IndonesiaDivision of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, University of Indonesia,Cipto Mangunkusumo Hospital, Jakarta, IndonesiaDepartment of Anesthesiology and Intensive Care, University of Indonesia, Jakarta, 10430, IndonesiaBackground: 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.https://f1000research.com/articles/11-143/v2COVID-19 secretome mesenchymal stem cell cytokine inflammation mediatorseng |
| spellingShingle | Hary Sakti Muliawan Erlina Burhan Mia Elhidsi Heri Wibowo Triya Damayanti Jeanne Adiwinata Pawitan Isabella Kurnia Liem Ismail Hadisoebroto Dilogo Mira Yulianti Adityo Susilo Irandi Putra Pratomo Raden Rara Diah Handayani Rahyussalim - Murdani Abdullah Cosphiadi Irawan Robert Sinto Dita Aditianingsih Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial [version 2; peer review: 1 approved, 2 approved with reservations] F1000Research COVID-19 secretome mesenchymal stem cell cytokine inflammation mediators eng |
| title | Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial [version 2; peer review: 1 approved, 2 approved with reservations] |
| title_full | Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial [version 2; peer review: 1 approved, 2 approved with reservations] |
| title_fullStr | Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial [version 2; peer review: 1 approved, 2 approved with reservations] |
| title_full_unstemmed | Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial [version 2; peer review: 1 approved, 2 approved with reservations] |
| title_short | Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial [version 2; peer review: 1 approved, 2 approved with reservations] |
| title_sort | effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of covid 19 a randomized controlled trial version 2 peer review 1 approved 2 approved with reservations |
| topic | COVID-19 secretome mesenchymal stem cell cytokine inflammation mediators eng |
| url | https://f1000research.com/articles/11-143/v2 |
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