Histological evaluation of ovine mammary tissue xenografted into cyclosporine treated mice

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Virginia Tech

Cyclosporine (CsA), a fungal peptide with remarkable anti-lymphocytic properties, has been shown to be an effective immunosuppressive agent. In three separate experiments, mice receiving CsA at various doses (8 mg/kg/day in the first two experiments and 70-100 mg/kg/day in the third), were implanted with ovine mammary tissue expants at various sites (subcutaneous dorsum, ovarian fat-pad, and cleared mammary gland fat-pad). After different periods of time, (day 3, 7, 14, 21, and 35) implants were removed, fixed, stained, and embedded. Epithelial morphology of the implants was evaluated via a grading system that classified epithelium from 1 (poor) to 5 (excellent). Leukocyte type and number was determined in subepithelial stroma of implants in the third experiment. In the first two experiments, histological evaluation revealed that the transplanted tissue did not survive, regardless of site of implantation or developmental stage of donor tissue. In experiment three higher, dosages of CsA and different donor tissue were used, this resulted in significantly higher (P < .05) mean epithelial scores (indicative of healthier epithelium) for two CsA treated groups vs two control groups (3.75 and 2.33 vs 2.0 and 1.25, respectively). Within each treatment group (CsA and control), one group of mice received exogenous estrogen and progesterone (EjP) implants. CsA treated mice receiving E/P had significantly higher (P < .05) epithelial scores than those not receiving hormones (3.68 vs 2.83). The reverse was true for lymphocyte number (18.9 vs 40.5 cells per 117,600 um² of subepithelial stroma) which were significantly less in CsA + E/P treated mice. The overall correlation between lymphocyte number and epithelial score was -.55 (P < .0001). These results indicate that ovine mammary tissue xenografted into mice treated with high doses of CsA, are capable of surviving for extended periods of time (at least 35 days).