Endocrine Abstracts

Introduction: Uterine leiomyoma (fibroid) is the most common solid tumor in reproductive-age women. Symptomatic leiomyomas affect millions of women through menorrhagia, abnormal uterine bleeding, and infertility. No effective treatment except surgery is available, partly because of the lack of effective animal models for screening new therapies. We established a new xenograft model by grafting primary cultured leiomyoma cells beneath the kidney capsule in super-immunodeficient mice; however, this model is not suitable for screening tests because of the expensive host and difficult grafting procedure. To resolve these issues, we investigated whether this model could be replicated using different types of immunodeficient mice and grafting procedures.

Methods: All specimens were obtained from patients who had undergone hysterectomy for symptomatic leiomyomas. We primarily cultured leiomyoma smooth muscle cells and mixed them with type 1 collagen gel to form cell pellets. We then grafted the pellets beneath the kidney capsule in non-obese diabetic /severe combined immunodeficient (NOD/SCID) mice, SCID mice, and BALB/c nude mice. Next we grafted the pellets beneath the kidney capsule and subcutaneous space in NOD/SCID and NOD/SCID IL2Rγ null (NOG) mice. All mice were ovariectomized at the time of grafting, and both 17β-estradiol and progesterone were injected subcutaneously every week. Eight weeks later, we performed immunohistochemical evaluation of the xenografts with regard to their gross appearance, histology, and expression of estrogen and progesterone receptors.

Results: The xenografts beneath the kidney capsule were significantly enlarged in NOD/SCID mice compared with those in SCID or BALB/c nude mice. Furthermore, similar to subrenal xenografts, subcutaneous xenografts were enlarged in both NOD/SCID and NOG mice. Histologically, all enlarged xenografts within the mice mimicked human uterine leiomyomas and expressed both estrogen and progesterone receptors.

Conclusions: NOD/SCID mice are suitable hosts for the leiomyoma xenograft model. A subcutaneous xenograft is superior to a subrenal one. The easy grafting procedure can avoid the risk of intraoperative death of the host mice. The optimized xenograft model is suitable for screening new therapies that generally requires large number of subjects.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.