The Immunoregulatory and Regenerative Potential of Activated Human Stem Cell Secretome Mitigates Acute-on-Chronic Liver Failure in a Rat Model
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2024
Author(s)
Yael Diaz
Claudio Rivas
Cristobal Molina
Valeska Simon
Maria Rosa Bono
Bernardo Morales
Mario Rosemblatt
Sebastian Silva
Type
Resource Types::text::journal::journal article
Abstract
<jats:p>Acute-on-chronic liver failure (ACLF) is a syndrome marked by sudden liver function decline and multiorgan failure, predominantly acute kidney injury (AKY), in patients with chronic liver disease. Unregulated inflammation is a hallmark of ACLF; however, the key drivers of ACLF are not fully understood. This study explores the therapeutic properties of human mesenchymal stem cell (MSC) secretome, particularly focusing on its enhanced anti-inflammatory and pro-regenerative properties after the in vitro preconditioning of the cells. We evaluated the efficacy of the systemic administration of MSC secretome in preventing liver failure and AKI in a rat ACLF model where chronic liver disease was induced using by the administration of porcine serum, followed by D-galN/LPS administration to induce acute failure. After ACLF induction, animals were treated with saline (ACLF group) or MSC-derived secretome (ACLF-secretome group). The study revealed that MSC-secretome administration strongly reduced liver histological damage in the ACLF group, which was correlated with higher hepatocyte proliferation, increased hepatic and systemic anti-inflammatory molecule levels, and reduced neutrophil and macrophage infiltration. Additionally, renal examination revealed that MSC-secretome treatment mitigated tubular injuries, reduced apoptosis, and downregulated injury markers. These improvements were linked to increased survival rates in the ACLF-secretome group, endorsing MSC secretomes as a promising therapy for multiorgan failure in ACLF.</jats:p>
Cite this document
Cuadra, B., Silva, V., Huang, Y.-L., Diaz, Y., Rivas, C., Molina, C., Simon, V., Bono, M. R., Morales, B., Rosemblatt, M., Silva, S., Acuña, R., Ezquer, F., & Ezquer, M. (2024). The immunoregulatory and regenerative potential of activated human stem cell secretome mitigates acute-on-chronic liver failure in a rat model. International Journal of Molecular Sciences, 25(4), 2073. https://doi.org/10.3390/ijms25042073
Project(s)
Subjects
acute-on-chronic liver failure
;
in vitro preconditioning
;
mesenchymal stem cells
;
multiorgan failure
;
secretome