Endogenous origin of glomerular endothelial and mesangial cells in grafts of embryonic kidneys

Endogenous origin of glomerular endothelial and mesangial cells in grafts of embryonic kidneys
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DOI:
10.1152/ajprenal.1996.270.5.f886
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发表时间:
1996-05-01
影响因子:
4.2
通讯作者:
Abrahamson, DR
Abrahamson, DR
中科院分区:
医学2区
文献类型:
--
作者:
Hyink, DP;Tucker, DC;Abrahamson, DR

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为了解决肾小球内皮细胞和系膜细胞在胚胎哺乳动物肾脏的起源,我们建立了大鼠和小鼠之间的种间移植,其中胎儿肾脏植入到成年宿主的前眼房。5 - 7天后,携带移植物的宿主接受针对基质组分的种特异性单克隆抗体(MAbs)的静脉内注射。在所有情况下,肾小球基底膜和系膜基质标记仅供者来源的基质。此外,移植物内的微血管细胞外基质通常来自供体。为了直接检查肾小球内皮细胞和系膜细胞的起源,我们将正常小鼠胚胎妊娠11 - 12天(E11 - 12)的肾脏移植到宿主反向剪接受体26小鼠的前眼房中,这些小鼠是在每个细胞中表达β-半乳糖苷酶的转基因动物。当移植物被开发为β-半乳糖苷酶活性时,在外周血管中可以看到宿主细胞,但大多数肾小球内皮细胞是供体的,而不是宿主的。在肾小球中发现宿主来源的内皮细胞的地方,也存在供体内皮细胞。系膜细胞总是供体来源。当E11小鼠肾脏用内皮细胞特异性Bandeiraea simplicifolia isolectin B-4标记时,我们确定内皮细胞从后肾发生开始就存在。总之,这些证据表明,内源性肾脏来源的细胞几乎完全负责oculo中肾小球微血管的发育。来自宿主的外部血管虽然对移植物的维持很重要,但不是肾小球的主要贡献者。
To address origins of glomerular endothelial and mesangial cells in embryonic mammalian kidneys, we established interspecies grafts between rats and mice, in which fetal kidneys were implanted into the anterior eye chamber of adult hosts. After 5-7 days, hosts bearing grafts received intravenous injections with species-specific monoclonal antibodies (MAbs) to matrix components. In all cases, glomerular basement membranes and mesangial matrices labeled solely for donor-derived matrix. Additionally, microvessel extracellular matrices within grafts were usually of donor origin. To examine directly the origin of glomerular endothelial and mesangial cells, we grafted embryonic gestational days 11-12 (E11-12) kidneys from normal mice into anterior eye chambers of host reverse-orientation splice acceptor 26 mice, which are transgenic animals that express beta-galactosidase in every cell. When grafts were developed for beta-galactosidase activity, host cells were seen in peripheral vessels, but the majority of glomerular endothelial cells were of donor, not host, origin. Where host-derived endothelial cells were found in glomeruli, donor endothelial cells were present as well. Mesangial cells were always of donor origin. When E11 mouse kidneys were labeled with the endothelial cell-specific Bandeiraea simplicifolia isolectin B-4, We determined that endothelial cells are present from the inception of metanephrogenesis. Together, the evidence shows that cells of endogenous kidney origin were almost entirely responsible for development of the glomerular microvasculature in oculo. External vessels from the host, although important for graft maintenance, were not major contributors to the glomerulus.