BACKGROUND: Development of an auxiliary liver is of interest for treating several conditions. To examine whether an isolated intestinal segment will support development of a heterotopic auxiliary liver, we studied the fate of liver microfragments in rats. METHODS: Small intestinal segments with intact circulation were created, and the small intestinal mucosa was removed. The intestinal segments were filled with autologous liver microfragments, and animals were studied for various periods. RESULTS: Initially, liver microfragments were engulfed by a serosanguineous exudate enriched in polymorphonuclear leukocytes, suggesting an early granulation-type response. Transplanted liver fragments were subsequently reorganized and showed morphologic integrity with typical hepatic lobular organization. Transplanted tissue contained healthy hepatocytes with abundant glycogen content. Transplanted liver remained intact in the small intestine for up to 40 days, although at later times portal fibrosis and bile ductular proliferation were apparent, despite the absence of cholestasis or hepatocellular abnormalities. In contrast, instillation of liver microfragments in the peritoneal cavity led to rapid loss of tissue integrity and phagocytotic clearance of transplanted tissue. CONCLUSIONS: Small intestinal segments denuded of the mucosal layer can support heterotopically transplanted liver. Further development of this auxiliary liver system will provide insights into mechanisms concerning neo-organogenesis and into potential therapeutic applications of heterotopic liver in specific diseases.
BACKGROUND: Development of an auxiliary liver is of interest for treating several conditions. To examine whether an isolated intestinal segment will support development of a heterotopic auxiliary liver, we studied the fate of liver microfragments in rats. METHODS: Small intestinal segments with intact circulation were created, and the small intestinal mucosa was removed. The intestinal segments were filled with autologous liver microfragments, and animals were studied for various periods. RESULTS: Initially, liver microfragments were engulfed by a serosanguineous exudate enriched in polymorphonuclear leukocytes, suggesting an early granulation-type response. Transplanted liver fragments were subsequently reorganized and showed morphologic integrity with typical hepatic lobular organization. Transplanted tissue contained healthy hepatocytes with abundant glycogen content. Transplanted liver remained intact in the small intestine for up to 40 days, although at later times portal fibrosis and bile ductular proliferation were apparent, despite the absence of cholestasis or hepatocellular abnormalities. In contrast, instillation of liver microfragments in the peritoneal cavity led to rapid loss of tissue integrity and phagocytotic clearance of transplanted tissue. CONCLUSIONS: Small intestinal segments denuded of the mucosal layer can support heterotopically transplanted liver. Further development of this auxiliary liver system will provide insights into mechanisms concerning neo-organogenesis and into potential therapeutic applications of heterotopic liver in specific diseases.
Authors: Zurab Kakabadze; Lia Karalashvili; David Chakhunashvili; Necat Havlioglu; Merab Janelidze; Ann Kakabadze; Yogeshwar Sharma; Sanjeev Gupta Journal: Mater Sci Eng C Mater Biol Appl Date: 2018-12-10 Impact factor: 7.328