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

Hirotaka Masuda, Tetsuo Maruyama, Emi Hiratsu, Junichi Yamane, Akio Iwanami, Takashi Nagashima, Masanori Ono, Hiroyuki Miyoshi, Hirotaka James Okano, Mamoru Ito, Norikazu Tamaoki, Tatsuji Nomura, Hideyuki Okano, Yumi Matsuzaki, Yasunori Yoshimura
Proceedings of the National Academy of Sciences of the United States of America · 2007 · vol. 104(6) , pp. 1925–1930 · doi:10.1073/pnas.0604310104 · PMID:17261813 · PMC1794295 · W1981334082
article OA: green CC0 ⤵ 55 in-corpus citations
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Functional human endometrium was regenerated from dispersed endometrial cells in immunodeficient mice, exhibiting hormone-dependent changes and enabling noninvasive assessment via bioluminescence imaging.

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Abstract

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/gamma(c)(null) 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.

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Condition tags

endometriosis

MeSH descriptors

Endometrium Endometrium Interleukin Receptor Common gamma Subunit Interleukin Receptor Common gamma Subunit Severe Combined Immunodeficiency Severe Combined Immunodeficiency Adult Animals Endometrium Endometrium Female Humans Interleukin Receptor Common gamma Subunit Kidney Kidney Mice Mice, Inbred NOD Mice, Knockout Mice, SCID Middle Aged

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