Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation
Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation
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DOI：
10.1073/pnas.0404626101
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发表时间：
2004-08-10
影响因子：
11.1
通讯作者：
Horwitz, EM
中科院分区：
文献类型：
--
作者：
Dominici, M;Pritchard, C;Horwitz, EM
骨和骨髓是紧密排列的生理隔室，这表明这些组织可能代表着一个单一的功能单位，具有共同的骨髓前体细胞，可以同时产生成骨细胞和造血细胞。尽管单个骨髓来源的干细胞植入多系细胞的报道支持这一观点，但最近的证据对干细胞转分化的说法提出了质疑，从而质疑了多潜能造血/成骨前体细胞的存在。在小鼠中使用再繁殖试验，我们在这里展示了来自塑料非黏附人群的带有基因标记的可移植骨髓细胞可以同时产生功能成骨细胞/骨细胞和造血细胞。X和Y染色体的荧光原位杂交和培养的成骨细胞的核型分析证实了这些细胞的供体来源，并排除了他们通过融合过程产生的细胞。分子分析表明，在7种动物的克隆性造血细胞和骨祖细胞中都有一个共同的逆转录病毒整合位点，为这些表面上独立的细胞类型建立了共同的克隆起源。我们的发现表明，骨髓含有一种原始细胞，能够同时产生造血系和骨系。它的分离和鉴定可能会为遗传性骨病和骨损伤提供新的治疗方法。
Bone and bone marrow are closely aligned physiologic compartments, suggesting that these tissues may represent a single functional unit with a common bone marrow progenitor that gives rise to both osteoblasts and hematopoietic cells. Although reports of multilineage engraftment by a single marrow-derived stem cell support this idea, more recent evidence has challenged claims of stem cell transdifferentiation and therefore the existence of a multipotent hematopoietic/osteogenic progenitor cell. Using a repopulation assay in mice, we show here that gene-marked, transplantable marrow cells from the plastic-nonadherent population can generate both functional osteoblasts/osteocytes and hematopoietic cells. Fluorescent in situ hybridization for the X and Y chromosomes and karyotype analysis of cultured osteoblasts confirmed the donor origin of these cells and excluded their generation by a fusion process. Molecular analysis demonstrated a common retroviral integration site in clonogenic hematopoietic cells and osteoprogenitors from each of seven animals studied, establishing a shared clonal origin for these ostensibly independent cell types. Our findings indicate that the bone marrow contains a primitive cell able to generate both the hematopoietic and osteocytic lineages. Its isolation and characterization may suggest novel treatments for genetic bone diseases and bone injuries.