Extrahepatic stem cells mobilized from the bone marrow by the supplementation of branched‐chain amino acids ameliorate liver regeneration in an animal model

• DOI: 10.1111/jgh.12450
• Publication Date: 2013-11-14T02:50:49Z
• Authors: Takehiro Okabayashi; Yasuo Shima; Tatsuaki Sumiyoshi; Akihito Kozuki; Tatsuo Iiyama; Teppei Tokumaru; Tsutomu Namikawa; Takeki Sugimoto; Yuka Takezaki; Hiromichi Maeda; Michiya Kobayashi; Kazuhiro Hanazaki
• Keywords: 0301 basic medicine; Time Factors; Stem Cells; Administration, Oral; Bone Marrow Cells; Cell Differentiation; Stimulation, Chemical; Liver Regeneration; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Liver; Models, Animal; Hepatocytes; Animals; Amino Acids, Branched-Chain; Cells, Cultured; Cell Proliferation; Stem Cell Transplantation

AbstractBackground and AimsIn recent years, bone marrow (BM)‐derived stem cell repopulation of injured organs has been increasingly observed; however, the extent to which it occurs and its clinical relevance remain unclear. Here, we investigated on the potential of extrahepatic stem cells to become hepatocytes using the treatment of the oral supplementation of branched‐chain amino acids (BCAA).MethodsIn the first, Sprague–Dawley (SD) rats were administered BCAA to promote liver regeneration; in the second, syngenic liver transplantations using wild‐type SD rats that do not express green fluorescent protein (GFP) as syngenic donors and GFP‐transgenic SD rats as recipients to confirm that an extrahepatic source of cells (GFP+) could repopulate the transplanted (GFP–) liver were performed.ResultsTreatment of the oral supplementation of BCAA for 2–3 weeks before transplantation to promote liver regeneration resulted in greater than 7 days graft volume, with extensive spotty conversion of a small wild‐type graft to the recipient GFP+ genotype. The treatment by oral supplementation of BCAA resulted in higher levels of CD34+SDF+c‐kit+ stem cells in the blood and liver after liver transplantation. Liver repopulation could be achieved with hepatocytes that bone marrow‐derived from stem cells proliferated.ConclusionsWe have identified extrahepatic stem cell migration from the BM to the injured liver as a mechanism underlying liver regeneration that supports hepatocyte proliferation in diseased liver. Our results suggested that BCAA is able to mobilize a population of BM‐derived cells that contribute to hepatic regeneration.