Cirrhotic Liver Sustains In Situ Regeneration of Acellular Liver Scaffolds after Transplantation into G-CSF-Treated Animals

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 7; p. 976
• Main Authors: Dias, Marlon Lemos, Wajsenzon, Inês Julia Ribas, Alves, Gabriel Bastos Naves, Paranhos, Bruno Andrade, Andrade, Cherley Borba Vieira, Siqueira Monteiro, Victoria Regina, de Sousa, Raysa Maria Reis, da Silva Pereira, Evelyn Nunes Goulart, Rodrigues, Karine Lino, Daliry, Anissa, Mello, Debora Bastos, Coeli Dos Santos Goldenberg, Regina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-03-2023; MDPI
• Subjects: Animals; Bile ducts; Biopsy; Blood circulation; Bone marrow; Care and treatment; Catheters; Cell activation; Cell growth; Colony-stimulating factor; decellularized extracellular matrix; decellularized liver; Drinking water; ductular reaction; Extracellular matrix; G-CSF; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - pharmacology; Granulocytes; Hematology; Hepatectomy; Hepatocytes; Hepatocytes - physiology; Immune response; in vivo recellularization; Inflammation; Leukocytes (granulocytic); Liver; Liver cirrhosis; Liver Cirrhosis - therapy; Liver diseases; Liver transplantation; Metabolism; Patient outcomes; Phenols; Progenitor cells; Rats; Regeneration; Tissue Scaffolds; Transplantation; Veins & arteries; Brazil; United States > US; Rio de Janeiro Brazil; decellularized extracellular matrix; liver fibrosis; tissue engineering; decellularized liver; in vivo recellularization; ductular reaction; G-CSF; liver regeneration; liver cirrhosis
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12070976

Acellular liver scaffolds (ALS) produced by decellularization have been successfully explored for distinct regenerative purposes. To date, it is unknown whether transplanted ALSs are affected by cirrhotic livers, either becoming cirrhotic themselves or instead remaining as a robust template for healthy cell growth after transplantation into cirrhotic rats. Moreover, little is known about the clinical course of recipient cirrhotic livers after ALS transplantation. To address these questions, we transplanted ALSs into cirrhotic rats previously treated with the granulocyte colony-stimulating factor. Here, we report successful cellular engraftment within the transplanted ALSs at 7, 15, and 30 days after transplantation. Recellularization was orchestrated by liver tissue cell activation, resident hepatocytes and bile duct proliferation, and an immune response mediated by the granulocyte components. Furthermore, we showed that transplanted ALSs ensured a pro-regenerative and anti-inflammatory microenvironment, attracted vessels from the host cirrhotic tissue, and promoted progenitor cell recruitment. ALS transplantation induced cirrhotic liver regeneration and extracellular matrix remodeling. Moreover, the transplanted ALS sustained blood circulation and attenuated alterations in the ultrasonographic and biochemical parameters in cirrhotic rats. Taken together, our results confirm that transplanted ALSs are not affected by cirrhotic livers and remain a robust template for healthy cell growth and stimulated cirrhotic liver regeneration.