OBJECTIVE-This study was undertaken to develop a representative murine model for human leiomyoma.STUDY DESIGN-Human fibroid tumor tissues were cut into small pieces and treated with medium alone, adenoviral-β-galactosidase, adenoviral-vascular endothelial growth factor-A, adenoviral-cyclooxygenase-2, or both adenoviral-vascular endothelial growth factor-A and adenoviral-cyclooxygenase-2. Tissue pieces were inserted subcutaneously in the flank of each severe combined immunodeficient mouse. The developed lesion was measured twice per week. Xenograft tissues were harvested after 30 days and analyzed.RESULTS-Tissue pieces transfected with both adenoviral-cyclooxygenase-2 and adenoviralvascular endothelial growth factor-A continued to grow up to 30 days postimplantation. The number of proliferating and apoptotic cells, as well as the expression of smooth muscle actin, desmin, vimentin, estrogen receptors, and progesterone receptors was similar between retrieved grafts from that group and the original patient tissue. Furthermore, hematoxylin and eosin and Masson's Trichrome stains confirmed this similarity.CONCLUSION-Human uterine leiomyoma xenografts, pretreated with both adenoviralcyclooxygenase-2 and adenoviral-vascular endothelial growth factor-A and implanted subcutaneously in severe combined immunodeficient mice, represent a novel model for human uterine leiomyoma. Uterine leiomyomas, commonly referred to as fibroids, are benign tumors that arise in the myometrial compartment of the uterus. 1 Leiomyomas are well-differentiated smooth muscle tumors with a relatively low mitotic index 1 ; tumors can become quite large and are usually multiple. Uterine leiomyomas are the most common gynecologic neoplasm, occurring in more than 70% of reproductive-age women. 1 When symptomatic, leiomyomas are associated with infertility, menorrhagia, and spontaneous abortion. They are the leading indication for hysterectomy in premenopausal women. 1 The high frequency of these tumors and lack of satisfactory nonsurgical and fertility-preserving treatments make uterine leiomyomas a significant reproductive health concern for women. 1 The underlying causes of uterine leiomyomas are poorly understood, as a result, in part, of the absence of a good model system with which to study these tumors. The only available animal model is the Eker rat in which both leiomyosarcomas and leiomyomas are observed. 2 Female Eker rats have uterine leiomyomas develop by 12 to 16 months of age with a frequency of about 65%. 2 The predisposing genetic alteration in these animals is an insertion of an endogenous retrovirus between exons 30 and 31 of the Tsc-2 gene, which inactivates the encoded tumor suppressor protein. This leads to the development of tumors in several different organs, such as the spleen, kidneys, lungs, and uterus. 2 Although the Eker rat has been valuable as an animal model for uterine leiomyoma, there are limitations regarding difficulty in breeding, low penetrance, high cost, and sarcoma-like histology that hinder its use as a...