Additional B-cell deficiency does not affect growth and angiogenesis of ectopic human endometrium in T-cell-deficient endometriosis mouse models during long-term culture

摘要

Heterologous endometriosis mouse models characterized by transplantation of human endometrial tissue into immunodeficient mice are widely used to develop novel treatment strategies for this gynecological disease. The majority of these experiments have been performed for up to one month in athymic T-cell-deficient nude mice, which, however, still exhibit intact B-lymphocytes possibly affecting growth and persistence of the xenografts. We describe here the heterologous mouse models used so far and comparatively analyze the characteristics of human endometrial tissue after subcutaneous and intraperitoneal transplantation in nude and in Rag-1-deficient mice exhibiting T- and B-cell deficiency. Moreover, we extended the time of culturing to three months in both mouse strains. Size, histomorphology, and vascularization of xenografts of intraperitoneal and subcutaneous localization did not differ significantly nor did those of the two immunodeficient mouse strains for up to three months of culturing. Whereas the rate of lesions was similar at both localizations in nude mice, in Rag-1 knockout mice significantly more intraperitoneal than subcutaneous lesions could be recovered. Interestingly, in both mouse strains a considerable number of xenografts completely invaded the peritoneal lining after intraperitoneal transplantation and could only be recovered histomorphologically. This has to be taken into account in studies depending on the quantitative analysis of ectopic peritoneal lesions. In conclusion, T-cell deficiency seems to be sufficient for the long-term culture of human endometrial tissue in subcutaneous and intraperitoneal localizations. Additional B-cell deficiency does not provide advantages with regard to the maintenance, morphology, and blood vessel supply of the ectopic endometrial lesions.