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Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/γcnull immunodeficient mice

机译:NOD / SCID /γcnull免疫缺陷小鼠重建功能性人子宫内膜的无创实时评估

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摘要

Human uterine endometrium exhibits unique properties of cyclical regeneration and remodeling throughout reproductive life and also is subject to endometriosis through ectopic implantation of retrogradely shed endometrial fragments during menstruation. Here we show that functional endometrium can be regenerated from singly dispersed human endometrial cells transplanted beneath the kidney capsule of NOD/SCID/γcnull immunodeficient mice. In addition to the endometrium-like structure, hormone-dependent changes, including proliferation, differentiation, and tissue breakdown and shedding (menstruation), can be reproduced in the reconstructed endometrium, the blood to which is supplied predominantly by human vessels invading into the mouse kidney parenchyma. Furthermore, the hormone-dependent behavior of the endometrium regenerated from lentivirally engineered endometrial cells expressing a variant luciferase can be assessed noninvasively and quantitatively by in vivo bioluminescence imaging. These results indicate that singly dispersed endometrial cells have potential applications for tissue reconstitution, angiogenesis, and human–mouse chimeric vessel formation, providing implications for mechanisms underlying the physiological endometrial regeneration during the menstrual cycle and the establishment of endometriotic lesions. This animal system can be applied as the unique model of endometriosis or for other various types of neoplastic diseases with the capacity of noninvasive and real-time evaluation of the effect of therapeutic agents and gene targeting when the relevant cells are transplanted beneath the kidney capsule.
机译:人子宫内膜在整个生殖生命中表现出周期性的再生和重塑的独特特性,并且在月经期间通过异位植入逆行脱落的子宫内膜碎片而遭受子宫内膜异位症。在这里,我们显示功能性子宫内膜可从单分散的人子宫内膜细胞再生而来,该人子宫内膜细胞移植于NOD / SCID /γcnull免疫缺陷小鼠的肾囊下方。除子宫内膜样结构外,可在重建的子宫内膜中复制激素依赖性变化,包括增殖,分化,组织分解和脱落(月经),血液主要由侵入小鼠的人血管提供肾实质。此外,可以通过体内生物发光成像非侵入性和定量地评估从表达变体荧光素酶的慢病毒工程子宫内膜细胞再生的子宫内膜的激素依赖性行为。这些结果表明,单分散的子宫内膜细胞可能在组织重建,血管生成和人-鼠嵌合血管形成中具有潜在的应用,为月经周期和形成子宫内膜异位病变的生理性子宫内膜再生的潜在机制提供了启示。这种动物系统可以用作子宫内膜异位症的独特模型,也可以用于其他各种类型的赘生性疾病,并且可以在将相关细胞移植到肾囊下方时对治疗剂和基因靶向进行无创和实时评估。

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