Maintenance and Repair of the Lung Endothelium Does Not Involve Contributions from Marrow-Derived Endothelial Precursor Cells

Maintenance and Repair of the Lung Endothelium Does Not Involve Contributions from Marrow-Derived Endothelial Precursor Cells
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DOI:
10.1165/rcmb.2011-0180oc
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发表时间:
2012-07-01
影响因子:
6.4
通讯作者:
Kotton, Darrell N.
Kotton, Darrell N.
中科院分区:
医学1区
文献类型:
--
作者:
Ohle, Sarah J.;Anandaiah, Asha;Kotton, Darrell N.

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肺内皮被认为是一种静止的组织,具有在损伤后表现出快速和有效修复的潜力。骨髓来源的内皮祖细胞被认为是新内皮细胞的来源之一,可直接促进肺内皮细胞的稳态和修复。在这里,我们使用骨髓移植模型,使用纯化的造血干细胞(HSC)或未分级的全骨髓,来评估细胞在各种组织内皮中的植入。我们发现,在稳定状态下或从高氧诱导的内皮损伤中恢复后,骨髓来源的细胞对肺内皮有任何贡献的证据很少。尽管移植后在肺组织中可以发现来源于HSC的罕见的CD 452-/CD 311 +/VECadherin+骨髓源性细胞群,但这些细胞不易在定义肺内皮的解剖位置发现。此外,通过追踪从含有内皮谱系选择性报告基因(Tie 2-GFP)的供体转基因小鼠中获得的移植骨髓细胞,即使在11个月的长期随访期或从高氧肺内皮损伤中恢复后,也不能检测到骨髓来源的细胞对成年肺、肝、胰腺、心脏和肾内皮的贡献。我们的研究结果反对骨髓来源的细胞在肺血管内皮中的任何显著植入。
Lung endothelium is believed to be a quiescent tissue with the potential to exhibit rapid and effective repair after injury. Endothelial progenitor cells derived from the bone marrow have been proposed as one source of new endothelial cells that may directly contribute to pulmonary endothelial cell homeostasis and repair. Here we use bone marrow transplantation models, using purified hematopoietic stem cells (HSCs) or unfractionated whole marrow, to assess engraftment of cells in the endothelium of a variety of tissues. We find scant evidence for any contribution of bone marrow-derived cells to the pulmonary endothelium in the steady state or after recovery from hyperoxia-induced endothelial injury. Although a rare population of CD452-/CD311+/VECadherin+ bone marrow-derived cells, originating from HSCs, can be found in lung tissue after transplantation, these cells are not readily found in anatomic locations that define the pulmonary endothelium. Moreover, by tracking transplanted bone marrow cells obtained from donor transgenic mice containing endothelial lineage-selective reporters (Tie2-GFP), no contribution of bone marrow-derived cells to the adult lung, liver, pancreas, heart, and kidney endothelium can be detected, even after prolonged follow-up periods of 11 months or after recovery from hyperoxic pulmonary endothelial injury. Our findings argue against any significant engraftment of bone marrow-derived cells in the pulmonary vascular endothelium.