A novel stem-cell population in adult liver with potent hematopoietic-reconstitution activity
A novel stem-cell population in adult liver with potent hematopoietic-reconstitution activity
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DOI：
10.1182/blood-2005-03-1017
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发表时间：
2005-09-01
期刊：
影响因子：
20.3
通讯作者：
Mulligan, RC
中科院分区：
文献类型：
--
作者：
Kotton, DN;Fabian, AJ;Mulligan, RC
最近的一些报道已经证明，具有造血重建能力的细胞可以从成年动物的各种实体器官中鉴定和分离。然而，在迄今为止的所有研究中，纯化的器官来源的干细胞表现出相对于纯化的骨髓来源的造血干细胞（BM HSC）的再生能力降低。因此，目前尚不清楚器官来源的HSC是否具有与BM HSC不同的功能特性，或者只是没有被纯化到相当的程度。在这里，我们报告了成年小鼠肝脏中一种罕见的细胞亚群的鉴定，这些细胞具有强大的血液再生潜力，接近BM HSC。基于染料流出活性和CD 45表达分离的细胞（称为CD 45（+）肝侧群[SP]尖端细胞）表现出与来自正常成年动物的新鲜分离的BM HSC相似的表面表型，但在表型上不同，因为它们不表达干细胞标记物c-kit。单细胞移植研究表明，CD 45（+）肝SP尖端细胞可以从骨髓造血干细胞中产生，这表明肝脏和骨髓室中的干细胞群之间存在关系。总的来说，这些研究对理解髓外造血有重要意义，并可能与目前旨在诱导移植器官耐受的策略有关。
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 that 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 side population [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 extramedullary hematopoiesis, and may be relevant to current strategies aimed at inducing tolerance to transplanted organs.