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骨髓移植后,造血细胞和成骨细胞来源于共同的骨髓祖细胞。

Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation.

作者信息

Dominici Massimo, Pritchard Colin, Garlits John E, Hofmann Ted J, Persons Derek A, Horwitz Edwin M

机构信息

Division of Experimental Hematology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.

出版信息

Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11761-6. doi: 10.1073/pnas.0404626101. Epub 2004 Jul 28.

Abstract

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.

摘要

骨骼和骨髓是紧密相连的生理腔室,这表明这些组织可能代表一个单一的功能单元,具有共同的骨髓祖细胞,可产生成骨细胞和造血细胞。尽管关于单个骨髓来源干细胞的多谱系植入的报道支持了这一观点,但最近的证据对干细胞转分化的说法提出了质疑,因此也对多能造血/成骨祖细胞的存在提出了质疑。通过在小鼠中进行的再增殖试验,我们在此表明,来自可塑性非贴壁群体的基因标记、可移植骨髓细胞能够产生功能性成骨细胞/骨细胞和造血细胞。对X和Y染色体进行荧光原位杂交以及对培养的成骨细胞进行核型分析,证实了这些细胞的供体来源,并排除了它们通过融合过程产生的可能性。分子分析表明,在所研究的七只动物中的每一只动物的克隆造血细胞和骨祖细胞中都存在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确立了共同的克隆起源。我们的研究结果表明,骨髓中含有一种能够产生造血和骨细胞谱系的原始细胞。对其进行分离和表征可能会为遗传性骨疾病和骨损伤提出新的治疗方法。

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