Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/gamma c(null) immunodeficient mice.
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.
Masuda
Hirotaka
H
Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Maruyama
Tetsuo
T
Hiratsu
Emi
E
Yamane
Junichi
J
Iwanami
Akio
A
Nagashima
Takashi
T
Ono
Masanori
M
Miyoshi
Hiroyuki
H
Okano
Hirotaka James
HJ
Ito
Mamoru
M
Tamaoki
Norikazu
N
Nomura
Tatsuji
T
Okano
Hideyuki
H
Matsuzaki
Yumi
Y
Yoshimura
Yasunori
Y
D000328:Adult; D000818:Animals; D004717:Endometrium / Q000473:pathology / Q000502:physiology* / Q000637:transplantation*; D005260:Female; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency* / Q000235:genetics*; D007668:Kidney / Q000098:blood supply; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008875:Middle Aged; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D014183:Transplantation, Heterologous / Q000295:instrumentation / Q000379:methods; D014741:Video Recording
D053631:Interleukin Receptor Common gamma Subunit