The Immunoregulatory and Regenerative Potential of Activated Human Stem Cell Secretome Mitigates Acute-on-Chronic Liver Failure in a Rat Model.
Barbara CuadraVeronica SilvaYa-Lin HuangYael DiazClaudio RivasCristobal MolinaValeska SimonMaría Rosa BonoBernardo MoralesMario RosemblattSebastian SilvaRodrigo A AcuñaFernando EzquerMarcelo EzquerPublished in: International journal of molecular sciences (2024)
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.
Keyphrases
- liver failure
- hepatitis b virus
- anti inflammatory
- stem cells
- acute kidney injury
- oxidative stress
- mesenchymal stem cells
- endothelial cells
- drug induced
- cell cycle arrest
- cell death
- induced apoptosis
- high glucose
- single cell
- adipose tissue
- induced pluripotent stem cells
- signaling pathway
- cardiac surgery
- ischemia reperfusion injury
- inflammatory response
- extracorporeal membrane oxygenation
- respiratory failure
- combination therapy
- aortic dissection