Jiang Shuguang, Walker Luke, Afentoulis Michael, Anderson Daniel A, Jauron-Mills Linda, Corless Christopher L, Fleming William H
Center for Hematologic Malignancies, Division of Hematology and Medical Oncology, Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA.
Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16891-6. doi: 10.1073/pnas.0404398101. Epub 2004 Nov 17.
Recent evidence indicates that bone marrow is a source of endothelial progenitor cells that are mobilized into the peripheral blood in response to cytokines or tissue injury. Previously, we showed that functional endothelial cells (ECs) can be clonally derived from phenotypically defined hematopoietic stem cells. To determine the EC potential of human bone marrow and peripheral blood stem cells, blood vessels in sex-mismatched transplant recipients were evaluated. EC outcomes were identified by using a combination of immunohistochemistry and XY interphase FISH. Donor-derived ECs were detected in the skin and gut of transplant recipients with a mean frequency of 2% and could readily be distinguished from CD45-expressing hematopoietic stem cells. None of the >4,000 ECs examined had more than two sex chromosomes, consistent with an absence of cell fusion. Y chromosome signals were not detected in sex-matched female recipients, excluding the vertical transmission of male cells. None of the recipients evaluated before hematopoietic engraftment demonstrated donor-derived ECs, indicating a close linkage between the recovery of hematopoiesis and EC outcomes. Transplantable bone marrow-derived endothelial progenitor cells may represent novel therapeutic targets for hematopoietic and vascular disease.
最近的证据表明，骨髓是内皮祖细胞的一个来源，这些细胞会响应细胞因子或组织损伤而被动员到外周血中。此前，我们表明功能性内皮细胞（ECs）可以从表型明确的造血干细胞中克隆获得。为了确定人类骨髓和外周血干细胞的内皮细胞潜能，我们评估了性别不匹配的移植受者体内的血管。通过免疫组织化学和XY间期荧光原位杂交相结合的方法来鉴定内皮细胞的结果。在移植受者的皮肤和肠道中检测到供体来源的内皮细胞，平均频率为2%，并且很容易与表达CD45的造血干细胞区分开来。在检查的4000多个内皮细胞中，没有一个细胞的性染色体超过两条，这与不存在细胞融合的情况一致。在性别匹配的女性受者中未检测到Y染色体信号，排除了雄性细胞的垂直传递。在造血植入前评估的受者中，没有一个显示出供体来源的内皮细胞，这表明造血恢复与内皮细胞结果之间存在密切联系。可移植的骨髓来源的内皮祖细胞可能代表造血和血管疾病的新型治疗靶点。
