Nonobese diabetic severecombined immunodeficient murine xenograft model for human uterine leiomyoma

Capsule:
We established a novel NOD/SCID murine xenograft model for uterine leiomyoma that reproduced histologic characteristics, sex steroid–dependent growth, and specific gene expression profiles of the original leiomyoma tissue.

Authors:
Guiwen Wang, M.D., Hiroshi Ishikawa, M.D., Ph.D., Kunizui Sone, M.D., Tatsuya Kobayashi, M.S., Ji-Yong J. Kim, Ph.D., Takeshi Kurita, Ph.D., Makio Shozu, M.D., Ph.D.

Volume 101, Issue 5, Pages 1485–1492.e3

Abstract:

Objective:
To establish a novel xenograft model using a severely immunocompromised host that is more convenient for uterine leiomyoma research compared with a pre-existing model using nonobese diabetic/severe combined immunodeficient (NOD/SCID) IL-2Rγ-null mice.

Design:
Experimental study.

Setting:
University and an attached animal facility.

Animal(s):
NOD/SCID, SCID, BALB/c nude, and NOD/SCID IL-2Rγ-null mice.

Intervention(s):
Xenografts consisting of primary cultured leiomyoma and myometrial cells in the subrenal and subcutaneous (SC) spaces in ovariectomized mice, followed by sex steroids (estrogen and P) administration.

Main Outcome Measure(s):
Viability, volume, histology, and sex steroid receptor expression of xenografts in response to sex steroid administration, to evaluate feasibility of the model; and messenger RNA expression levels of 12 genes representative of leiomyoma in the xenografts, to characterize the model.

Result(s):
Leiomyoma xenografts increased in volume at the highest frequency (55.1%) in response to sex steroids in NOD/SCID mice. Xenografts reproduced the histology and maintained expression of sex steroids receptors and representative genes of the original tissues. Subrenal xenografts were significantly larger than the SC xenografts, whereas those consisting of myometrial cells never increased.

Conclusion(s):
The modified NOD/SCID murine subrenal leiomyoma xenograft model reproduced most characteristics of the original leiomyoma tissue. Our model provides a more convenient research tool to investigate the pathogenesis of uterine leiomyoma.

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