Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Promotes Liver Regeneration and Anti-Fibrotic Effect in Liver Fibrosis Animal Model.

<b>Background and Objective:</b> Liver fibrosis (LF) is a most common pathological process characterized by the activation of hepatocytes leading to the accumulation of extracellular matrix (ECM). Hypoxia precondition treated in MSCs (H-MSCs) could enhance their immunomodulatory and regeneration capability, through expressing robust anti-inflammatory cytokines and growth factors, known as H-MSCs secretome (SH-MSCs) that are critical for the improvement of liver fibrosis. However, the study regarding the efficacy and mechanism of action of SH-MSCs in ameliorating liver fibrosis is still inconclusive. In this study, the therapeutic potential and underlying mechanism for SH-MSCs in the treatment of liver fibrosis were investigated. <b>Materials and Methods:</b> A rat model with liver fibrosis induced by CCl₄ was created and maintained for 8 weeks. The rats received intravenous doses of SH-MSCs and secretome derived from normoxia MSCs (SN-MSCs), filtered using a tangential flow filtration (TFF) system with different molecular weight cut-off categories, both at a dosage of 0.5 mL. The ELISA assay was employed to examine the cytokines and growth factors present in both SH-MSCs and SN-MSCs. On the ninth day, the rats were euthanized and liver tissues were collected for subsequent histological examination and analysis of mRNA expression. <b>Results:</b> The ELISA test revealed that SH-MSCs exhibited higher levels of VEGF, PDGF, bFGF, IL-10, TGF-ß and IL-6 compared to SN-MSCs. <i>In vivo</i>, administration of SH-MSCs notably decreased mortality rates. It also demonstrated a reduction in liver fibrosis, collagen fiber areas, α-SMA positive staining and relative mRNA expression of TGF-ß. Conversely, SN-MSCs also contributed to liver fibrosis improvement, although SH-MSCs demonstrated more favorable outcomes. <b>Conclusion:</b> Current findings suggested that SH-MSCs could improve CCl₄-induced liver fibrosis and decrease α-SMA and TGF-ß expression.

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

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.