The human fetal lung xenograft: validation as model of microvascular remodeling in the postglandular lung.
The human fetal lung xenograft: validation as model of microvascular remodeling in the postglandular lung.
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DOI：
10.1002/ppul.22617
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发表时间：
2012-12
影响因子：
3.1
通讯作者：
Mao, Quanfu
中科院分区：
文献类型：
--
作者：
De Paepe, Monique E.;Chu, Sharon;Hall, Susan;Heger, Nicholas E.;Thanos, Chris;Mao, Quanfu
上皮和脉管系统的协调重建对于正常的腺后肺发育是必不可少的。人-啮齿动物异种肺移植作为胎儿微血管发育模型的价值仍然不明确。本研究的目的是确定胎肺异种移植物中内源性（人源性）微血管的命运。从自发性妊娠丢失（妊娠14-22周）中获得肺组织，并将其植入SCID-米色小鼠（T、B和NK细胞缺陷型）和/或裸大鼠（T细胞缺陷型）的肾包膜下或背侧皮下空间。获得了父母的知情同意。在移植后2周和4周通过光镜、免疫组化和基因表达研究评估肺形态发生、微血管生成和上皮分化。存档的年龄匹配的死后肺作为对照。SCID-beige小鼠肾被膜下移植物的血管形态、密度和增殖与年龄匹配的对照肺相似，保留了上皮和血管系统之间的生理联系。SCID-米色小鼠皮下移植物的微血管发育不全和畸形，与显著较低的VEGF，内皮糖蛋白，血管生成素-2 mRNA表达比肾移植物。两个部位的移植物均显示轻度的气腔发育不良。裸大鼠肾包膜下移植物表现出宿主淋巴细胞的频繁浸润和闭塞性细支气管炎样改变，与内源性血管生成显著减少相关。本研究表明，宿主和部位选择对确保最佳异种移植物发育至关重要。当移植到严重的免疫抑制，NK细胞缺陷的主机和移植在肾包膜下网站，人到啮齿类动物的胎肺异种移植提供了一个有效的模型后腺微血管肺重塑。
Coordinated remodeling of epithelium and vasculature is essential for normal postglandular lung development. The value of the human-to-rodent lung xenograft as model of fetal microvascular development remains poorly defined. The aim of this study was to determine the fate of the endogenous (human-derived) microvasculature in fetal lung xenografts. Lung tissues were obtained from spontaneous pregnancy losses (14–22 weeks’ gestation) and implanted in the renal subcapsular or dorsal subcutaneous space of SCID-beige mice (T, B and NK-cell-deficient) and/or nude rats (T-cell-deficient). Informed parental consent was obtained. Lung morphogenesis, microvascular angiogenesis and epithelial differentiation were assessed at two and four weeks post-transplantation by light microscopy, immunohistochemical and gene expression studies. Archival age-matched postmortem lungs served as control. The vascular morphology, density and proliferation of renal subcapsular grafts in SCID-beige mice were similar to age-matched control lungs, with preservation of the physiologic association between epithelium and vasculature. The microvasculature of subcutaneous grafts in SCID-beige mice was underdeveloped and dysmorphic, associated with significantly lower VEGF, endoglin, and angiopoietin-2 mRNA expression than renal grafts. Grafts at both sites displayed mild airspace dysplasia. Renal subcapsular grafts in nude rats showed frequent infiltration by host lymphocytes and obliterating bronchiolitis-like changes, associated with markedly decreased endogenous angiogenesis. This study demonstrates the critical importance of host and site selection to ensure optimal xenograft development. When transplanted to severely immune suppressed, NK-cell-deficient hosts and engrafted in the renal subcapsular site, the human-to-rodent fetal lung xenograft provides a valid model of postglandular microvascular lung remodeling.
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影响因子：
2.5
作者：
CASH, JM;REMMERS, EF;WILDER, RL
通讯作者：
WILDER, RL
DOI：
10.1165/rcmb.2004-0287oc
发表时间：
2005-05-01
影响因子：
6.4
作者：
McGrath-Morrow, SA;Cho, C;Tuder, RM
通讯作者：
Tuder, RM
影响因子：
9.8
作者：
Makanya, Andrew N.;Hlushchuk, Ruslan;Djonov, Valentin G.
通讯作者：
Djonov, Valentin G.
DOI：
10.1164/rccm.200608-1240oc
发表时间：
2008-07-15
影响因子：
24.7
作者：
De Paepe, Monique E.;Patel, Chintan;Mao, Quanfu
通讯作者：
Mao, Quanfu
影响因子：
15.9
作者：
Kasahara, Y;Tuder, RM;Voelkel, NF
通讯作者：
Voelkel, NF