Hum. Reprod. Advance Access originally published online on April 23, 2007
Human Reproduction 2007 22(7):1899-1906; doi:10.1093/humrep/dem085
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Xenotransplantation of testicular tissue into nude mice can be used for detecting leukemic cell contamination
1 Department of Women and Child Health, Astrid Lindgren Children's Hospital, Pediatric Endocrinology Unit, Q2:08, Karolinska Institute and University Hospital, SE-171 76 Stockholm, Sweden 2 Department of Medicine, Division of Hematology, Karolinska Institute and University Hospital, 171 76, Stockholm, Sweden 3 Childhood Cancer Research Unit, Karolinska Institute and University Hospital, 171 76, Stockholm, Sweden 4 Department of Pediatrics, University of Turku, 20520 Turku, Finland
5 Correspondence address. Tel: +46 8 51772507; Fax: +46 8 51775128; E-mail: mi.hou{at}ki.se
BACKGROUND: Xeno-grafting of testicular tissue may allow viable gamete maturation. This would be beneficial for prepubertal cancer patients in that it may allow restoration of fertility without the risk of a cancer relapse. However it is unknown whether cancer cells in the testicular graft can transmit the malignancy into the host animal and also if gametes can be retrieved from testicular grafts that are contaminated with malignant cells.
METHODS: Rat T-cell leukemia was employed as the source of leukemic lymphoblasts and testicular tissue. This was injected i.p. (lymphoblasts) or grafted s.c. (fresh or cryopreserved testicular tissue) into the back skin of intact nude mice. To simulate clinical autografting, testicular tissue was also transplanted into healthy piebald variegated (PVG) rats.
RESULTS: 50–70% of the mice, receiving 200 or 6000 leukemic lymphoblasts, developed terminal leukemia. All mice, grafted with either fresh or cryopreserved testicular tissue from leukemic donor, developed generalized leukemia and/or local tumors. All syngenic PVG rats, treated in the same manner, died of generalized leukemia. In all of the retrieved leukemic grafts, rat spermatogenesis was destroyed and only leukemic infiltration was detected.
CONCLUSIONS: Grafting testicular tissue contaminated with leukemic cells led to tumor growth at the injection site without potential to differentiate germline stem cells into gametes. Xenografting could provide a novel functional strategy for simultaneous detection of malignant cell contamination and spermatogonial potential in testicular xenografts collected for fertility preservation.
Key words: Lymphoblastic leukemia/nude mouse/rat/testis/xenotransplantation
Submitted on January 30, 2007; resubmitted on February 28, 2007; accepted on March 5, 2007.
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