Flow–Cytometric Separation and Enrichment of Hepatic Progenitor Cells in the Developing Mouse Liver

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Abstract
Stem cells responsible for tissue maintenance and repair are found in a number of organs. However, hepatic stem cells assumed to play a key role in liver development and regeneration remain to be well characterized. To address this issue, we set up a culture system in which primitive hepatic progenitor cells formed colonies. By combining this culture system with fluorescence–activated cell sorting (FACS), cells forming colonies containing distinct hepatocytes and cholangiocytes were identified in the fetal mouse liver. These cells express both CD49f and CD29 (α6 and β1 integrin subunits), but do not mark for hematopoietic antigens such as CD45, TER119, and c–Kit. When transplanted into the spleen, these cells migrated to the recipient liver and differentiated into liver parenchymal cells. Our data demonstrate that hepatic progenitor cells are enriched by FACS and suggest approaches to supplanting organ allografting and improving artificial–organ hepatic support.
Funding Information
  • Grant-in-aid for Developmental Scientific Research, The Ministry of Education, Science and Culture
  • “Research for the Future” Program
  • Japan Society for the Promotion of Science (JSPS) (JSPS-RFTF96I00202)
  • CREST of Japan Science and Technology Corporation (JST)
  • Uehara Memorial Foundation, the Kanehara Ichiro Memorial Foundation, the Cell Science Research Foundation
  • Organized Research Combination System from the Science and Technology Agency of Japan