Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment
Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment
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DOI：
10.1182/blood-2005-06-2211
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发表时间：
2006-03-01
期刊：
影响因子：
20.3
通讯作者：
Ando, K
中科院分区：
文献类型：
--
作者：
Muguruma, Y;Yahata, T;Ando, K
造血是通过造血细胞和非造血细胞之间的特异性相互作用来维持的。尽管造血干细胞（HSC）已在体外和体内进行了广泛的研究，但对非造血成分的干细胞（称为间充质干细胞（MSC））的体内特性知之甚少。在这里，我们已经可视化和特点的人骨髓间充质干细胞在体内髓内移植增强绿色荧光蛋白标记的人骨髓间充质干细胞（eGFP-MSCs）到非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠的骨髓（BM）。移植后4至10周，移植到小鼠骨髓中的eGFP-MSC整合到宿主小鼠的造血微环境（HME）中。它们分化为周细胞、肌成纤维细胞、BM基质细胞、骨中的骨细胞、骨衬里成骨细胞和内皮细胞，这些细胞构成BM HME的功能组分。人骨髓间充质干细胞在小鼠骨髓中的存在导致在功能和表型上原始的人造血细胞的增加。重建HME的人MSC衍生细胞似乎通过与原始人造血细胞积极相互作用而有助于维持人造血。
Hematopoiesis is maintained by specific interactions between both hematopoietic and nonhematopoietic cells. Whereas hematopoietic stem cells (HSCs) have been extensively studied both in vitro and in vivo, little is known about the in vivo characteristics of stem cells of the nonhematopoietic component, known as mesenchymal stem cells (MSCs). Here we have visualized and characterized human MSCs in vivo following intramedullary transplantation of enhanced green fluorescent protein-marked human MSCs (eGFP-MSCs) into the bone marrow (BM) of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Between 4 to 10 weeks after transplantation, eGFP-MSCs that engrafted in murine BM integrated into the hematopoietic microenvironment (HME) of the host mouse. They differentiated into pericytes, myofibroblasts, BM stromal cells, osteocytes in bone, bone-lining osteoblasts, and endothelial cells, which constituted the functional components of the BM HME. The presence of human MSCs in murine BM resulted in an increase in functionally and phenotypically primitive human hematopoietic cells. Human MSC-derived cells that reconstituted the HME appeared to contribute to the maintenance of human hematopolesis by actively interacting with primitive human hematopoietic cells.