Perivascular support of human hematopoietic stem/progenitor cells
Perivascular support of human hematopoietic stem/progenitor cells
复制标题
DOI：
10.1182/blood-2012-08-451864
复制
发表时间：
2013-04-11
期刊：
影响因子：
20.3
通讯作者：
Peault, Bruno
中科院分区：
文献类型：
--
作者：
Corselli, Mirko;Chin, Chee Jia;Peault, Bruno
造血干细胞和祖细胞（HSPCs）在卵黄囊、性腺-中肾区、胚胎肝脏和胎儿骨髓中邻近血管壁出现和发育。在成年小鼠骨髓中，血管周围细胞形成HSPC的"小生境"。间充质干/基质细胞（MSC），支持培养中的造血，本身部分来源于血管周围细胞。为了确定它们在造血中的直接作用，我们测试了纯化的人CD146（+）血管周围细胞与未分级的MSC和CD146（-）细胞相比在共培养中维持人HSPC的能力。CD146（+）血管周围细胞通过细胞间接触和至少部分通过Notch激活支持能够移植原发性和继发性免疫缺陷小鼠的人髓淋巴样HSPC的长期持续存在。相反，未分级的MSC和CD146（-）细胞诱导分化并损害HSPC的离体维持。此外，CD146（+）血管周围细胞表达，天然和在培养中，血管造血生态位的分子标志物。出乎意料的是，从非造血脂肪组织中提取的CD146（+）血管周围细胞中存在这种戏剧性的，以前没有记录的支持造血干细胞的能力。
Hematopoietic stem and progenitor cells (HSPCs) emerge and develop adjacent to blood vessel walls in the yolk sac, aorta-gonad-mesonephros region, embryonic liver, and fetal bone marrow. In adult mouse bone marrow, perivascular cells shape a "niche" for HSPCs. Mesenchymal stem/stromal cells (MSCs), which support hematopoiesis in culture, are themselves derived in part from perivascular cells. In order to define their direct role in hematopoiesis, we tested the ability of purified human CD146(+) perivascular cells, as compared with unfractionated MSCs and CD146(-) cells, to sustain human HSPCs in coculture. CD146(+) perivascular cells support the long-term persistence, through cell-to-cell contact and at least partly via Notch activation, of human myelolymphoid HSPCs able to engraft primary and secondary immunodeficient mice. Conversely, unfractionated MSCs and CD146(-) cells induce differentiation and compromise ex vivo maintenance of HSPCs. Moreover, CD146(+) perivascular cells express, natively and in culture, molecular markers of the vascular hematopoietic niche. Unexpectedly, this dramatic, previously undocumented ability to support hematopoietic stem cells is present in CD146(+) perivascular cells extracted from the nonhematopoietic adipose tissue.