Case series of the first three severe COVID-19 patients treated with the secretome of hypoxia-mesenchymal stem cells in Indonesia

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the outbreak of coronavirus disease 2019 (COVID-19), which has been rapidly spreading. Several guideline therapies have been proposed as a possible treatment for SARS-CoV-2, however, these therapies are not sufficient to treat a severe condition of SARS-CoV-2 infection characterised by the increase of D-dimer and C-reactive protein (CRP) levels, and patchy ground-glass opacities (GGOs). Secretome-mesenchymal stem cells (S-MSCs) produced by MSCs under hypoxia could excessively release several anti-inflammatory cytokines and growth factors to control the COVID-19 cytokine storm and accelerate lung injury improvement. This is the first study investigating the clinical outcomes of three severe COVID-19 patients admitted to the intensive care unit of three different hospitals in Indonesia treated with S-MSCs. The decrease of D-dimer and CRP level was reported for all patients treated with S-MSCs. This was in line with improvement of pulmonary radiology, blood gas level, and hematologic assessment. In conclusion, these cases suggest that S-MSCs could effectively control D-dimer, CRP level and GGOs of severe COVID-19 patients associated with recovered pulmonary function.

Effects of secretome supplementation on interleukin-6, tumor necrosis factor-α, procalcitonin, and the length of stay in acute exacerbation COPD patients

“…The decrease in IL-6 levels in the secretome treatment group of this study suggested that secretome might be supplemented as additional therapy in AECOPD patients. It was in accordance with a previous study which reported that administration of secretome at a dose of 1 ml/12 hours for three days can control inflammation in COVID-19 patients [18]. The elevated IL-6 level indicates a systemic inflammatory response such as dyspnea and lung function, and can be used as an early indicator of inflammation in infection [19].…”

“…The differences between the two groups were statistically significant, suggesting that secretome could reduce TNF-α levels in AECOPD patients. The decrease in the treatment group was in accordance with the previous study which reported that giving secretome at a dose of 1 ml/12 hours for three days could control inflammation in COVID-19 patients [18]. Another study showed that secretome and MSCs supplementation suppressed cytokine production, increased the expression of macrophage marker M2, and increased the phagocytic capacity of monocytederived macrophage (MDM) in acute respiratory distress syndrome (ARDS) mouse model [22].…”

“…Secretome administration is able to inhibit NF-κB activity and therefore it will inhibit the release of pro-inflammatory cytokines, including PCT [18]. It has been known that AECOPD patients had higher PCT values compared to the stable COPD [27,28] up to nine times [29].…”

Mesenchymal Stromal Cells for Enhancing Hematopoietic Engraftment and Treatment of Graft-Versus-Host Disease, Hemorrhages and Acute Respiratory Distress Syndrome

“…The exosomes were safe, and recovery was seen in 17 (71%) of the patients (141). A case study of 3 severe Covid-19 patients treated with concentrated secretomes of hypoxia-conditioned MSCs reported safety and beneficial effects (142).…”

The Potential of Moringa Leaf Extract to Prevent Aging Targeted Cellular Senescence

“…The expression of p21 protein causes cell cycle arrest in senescence [3][4][5] . The cell cycle termination condition that has been reached causes a gradual decrease in p21 expression followed by an increase in cyclin dependent kinase inhibitor to maintain senescence [6][7][8] . This p21 inhibitor through its antioxidant activity can suppress ROS levels is an important target to prevent the formation of senescence cells.…”