Maintaining Squamous Epithelial Architecture in a Human Cervical Epithelium to SCID Mouse Xenograft Model System

Abstract

Objective: To establish a mouse model system of human cervical epithelium that maintains the stratified squamous architecture overlying a well-defined basement membrane.

Methods: Normal cervical tissue specimens were obtained from the transformation zone of hysterectomy specimens. Small (2 mm) cubes of tissue containing stroma and epithelium were placed subdermally into severe combined immunodeficient (SCID) mice and harvested between 7 and 45 days. Specimens were examined histologically for the presence of stroma, epithelium, and basement membrane.

Results: In 49 xenograft attempts in 24 mice, 35 (71%) were identified microscopically. Of these, 28 (80%) had identifiable epithelium and 20 (57%) formed cysts lined with stratified squamous epithelium. A cuboidal basal layer clearly defined the basement membrane. Proliferation within the cyst epithelium was demonstrated by expression of the Ki67 proliferation marker and the presence of mitotic figures.

Conclusions: A human to mouse xenograft model system is described that maintains, in high yield, stratified squamous epithelium overlying a well-defined basement membrane. Advantages of this model system include the following: (1) The tissue originates from readily available human specimens; (2) A stratified squamous epithelial architecture is maintained for a sufficient time to study viral effects on proliferation; (3) The basement membrane of the epithelium is well defined, allowing for investigation of connective tissue factors in cervical intraepithelial neoplasia and cervical cancer.

Keywords

Human cervical epithelium model system SCID mice CIN model system

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