Synergistic Hepatoprotective Effects of Mesenchymal Stem Cells and Platelet-Rich Plasma in a Rat Model of Bile Duct Ligation-Induced Liver Cirrhosis

• Published in: Cells (Basel, Switzerland) Vol. 13; no. 5; p. 404
• Main Authors: Shivaramu, Shivaraju, Maiti, Swapan Kumar, Banu, Shajahan Amitha, Kalaiselvan, Elangovan, Sharun, Khan, Mishra, Mamta, Mohan, Divya, Palakkara, Sangeetha, Kumar, Sunil, Sahoo, Monalisa, Hescheler, Jürgen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.02.2024; MDPI
• Subjects: Abdomen; adipose-derived mesenchymal stem cells; Animals; Apoptosis; bile duct ligation; Bile ducts; Bile Ducts - metabolism; Blood & organ donations; Blood platelets; Body fat; Care and treatment; Cell proliferation; Cellular therapy; Chemokines; Cirrhosis; Collagen; Collagen - metabolism; Extracellular matrix; Fibrosis; Gallbladder diseases; Graft rejection; Growth factors; Health aspects; Hepatocyte growth factor; Humans; Immunomodulation; Ketamine; Laboratories; Liver; Liver cirrhosis; Liver Cirrhosis - metabolism; liver regeneration; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Platelet-rich plasma; Platelet-Rich Plasma - metabolism; Platelets; Progenitor cells; Public health; rat; Rats; Stem cells; Therapeutics, Experimental; Transplantation; Transplants & implants; Trophic factors; India; St Louis Missouri; United States > US; bile duct ligation; rat; liver regeneration; adipose-derived mesenchymal stem cells; liver cirrhosis
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13050404

Liver cirrhosis poses a global health challenge marked by significant prevalence and mortality. Current therapeutic options are limited by high costs and immune-mediated rejection, necessitating the exploration of innovative strategies to enhance hepatic self-rehabilitation, and counteract the underlying pathological mechanisms. We evaluated the hepatoprotective activity of rat adipose-derived mesenchymal stem cells (ADMSCs) in combination with platelet-rich plasma (PRP) and recombinant human hepatocyte growth factor (rh-HGF) on a rat model of liver fibrosis/cirrhosis induced by bile duct ligation (BDL). Treatment with PRP or rh-HGF alone did not yield significant hepatoprotection in the BDL-induced liver cirrhosis model. However, ADMSC transplantation alone exhibited the potential to alleviate impaired liver conditions. The combination of PRP and rh-HGF demonstrated superior ameliorative effects compared to either treatment alone. Notably, the combination of ADMSC + PRP or ADMSC + rh-HGF significantly enhanced hepatoprotective capacity compared to individual or combined PRP and rh-HGF therapies. Injection of ADMSC via the tail vein reduced inflammation, hepatocyte damage, and collagen deposition, improving overall liver function. This improvement was more pronounced when ADMSC was administered with PRP and rh-HGF versus monotherapy. Our study concludes that ADMSCs exert antifibrotic effects by inhibiting hepatic stellate cell proliferation, collagen synthesis, and inducing apoptosis. ADMSCs also demonstrate immune-modulatory effects and transdifferentiate into hepatic progenitor cells, secreting trophic factors, cytokines, and chemokines that promote impaired liver regeneration. The observed arrest in liver fibrosis progression highlights the potential therapeutic impact of these interventions.