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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1574-1580.
Prepublished online as a Blood First Edition Paper on May 3, 2005; DOI 10.1182/blood-2005-03-1017.
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Submitted March 14, 2005
Accepted April 21, 2005
A novel stem cell population in adult liver with potent hematopoietic reconstitution activity
Darrell N Kotton, Attila J Fabian, and Richard C Mulligan*
Department of Genetics, Harvard Medical School, Boston, MA, USA; Division of Molecular Medicine, Children's Hospital, Boston, MA, USA; Section of Pulmonary, Allergy, and Critical Care, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
Department of Genetics, Harvard Medical School, Boston, MA, USA; Division of Molecular Medicine, Children's Hospital, Boston, MA, USA
* Corresponding author; email: mulligan{at}receptor.med.harvard.edu.
A number of recent reports have documented that cells possessing hematopoietic reconstitution ability can be identified and isolated from a variety of solid organs in the adult animal. In all studies to date, however, purified organ-derived stem cells demonstrate a diminished repopulating capacity relative to that of purified bone marrow-derived hematopoietic stem cells (BM HSCs). It has therefore been unclear whether organ-derived HSCs possess functional properties distinct from those of BM HSCs, or simply have not been purified to a comparable extent. Here we report the identification of a rare subset of cells in adult murine liver which possess potent blood repopulating potential, approaching that of BM HSCs. The cells, isolated on the basis of dye-efflux activity and CD45 expression (termed CD45+ liver SP tip cells), exhibit a surface phenotype similar to that of freshly isolated BM HSCs derived from normal adult animals, but are phenotypically distinct in that they do not express the stem cell marker c-kit. Single cell transplantation studies indicate that CD45+ liver SP tip cells can be generated from BM HSCs, suggesting a relationship between stem cell populations in the liver and bone marrow compartments. Overall, these studies have important implications for understanding extra-medullary hematopoiesis, and may be relevant to current strategies aimed at inducing tolerance to transplanted organs.
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