Hematopoietic origins of fibroblasts: I. In vivo studies of fibroblasts associated with solid tumors

Hematopoietic origins of fibroblasts: I. In vivo studies of fibroblasts associated with solid tumors
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DOI:
10.1016/j.exphem.2005.10.009
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发表时间:
2006-02-01
影响因子:
2.6
通讯作者:
Drake, CJ
Drake, CJ
中科院分区:
医学4区
文献类型:
--
作者:
LaRue, AC;Masuya, M;Drake, CJ

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目标。最近的研究报道,骨髓细胞可以产生组织成纤维细胞。然而,产生成纤维细胞的骨髓细胞尚未被确定。在本研究中,我们在体内验证了组织成纤维细胞来源于造血干细胞(hsc)的假设。这些研究是在小鼠身上进行的,这些小鼠的造血功能是通过移植来自单个增强绿色荧光蛋白(EGFP)阳性HSC的克隆细胞群与小鼠肿瘤模型结合而重建的。当肿瘤在移植小鼠中增殖时,评估EGFP(+) hsc来源细胞的存在,发现两个突出的EGFP(+)细胞群。第一种细胞被确定为肿瘤间质囊内的成纤维细胞,其中一部分表达I型胶原mRNA和α -平滑肌肌动蛋白。第二种是与CD31(+)肿瘤血管相关的血管周围细胞。这些体内研究结果证实了成纤维细胞起源于HSC。(C) 2006国际实验血液学学会。Elsevier Inc.出版。
Objective. Recent studies have reported that bone marrow cells can give rise to tissue fibroblasts. However, the bone marrow cell(s) that gives rise to fibroblasts has not yet been identified. In the present study, we tested the hypothesis that tissue fibroblasts are derived from hematopoietic stem cells (HSCs) in vivo.Methods. These studies were conducted using mice whose hematopoiesis had been reconstituted by transplantation of a clonal population of cells derived from a single enhanced green fluorescent protein (EGFP)-positive HSC in conjunction with murine tumor models.Results. When tumors propagated in the transplanted mice were evaluated for the presence of EGFP(+) HSC-derived cells, two prominent populations of EGFP(+) cells were found. The first were determined to be fibroblasts within the tumor stromal capsule, a subset of which expressed type I collagen mRNA and alpha-smooth muscle actin. The second population was a perivascular cell associated with the CD31(+) tumor blood vessels.Conclusion. These in vivo findings establish an HSC origin of fibroblasts. (C) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.