Abstract 3038: Intra-testicular transplantation of purified autologous stem cells for treatment of chemotherapy-induced male infertility

Abstract

Abstract Post-chemotherapy-induced male infertility in patients with childhood cancers represents a major complication for long-term survivors. There is a significant risk for tissue damage in the seminiferous tubules, and subsequent impairment of spermatogenesis both in children and adult males who receive chemotherapy. These therapeutic regimens have deleterious effects on male fertility, resulting in the deficiency of functional spermatozoa. In adult males, fertility can be protected ahead of cancer treatment by cryopreservation of mature spermatozoa; however, this is not always possible in pre-puberty children. Autologous bone marrow stem cells (BMSCs) are suitable candidates for treating infertility after testicular exposure to low or moderate doses of chemotherapy due to their differentiation potentials into functional cell types that can promote spermatogenesis. In this report, we present a method for restoration of male fertility in post-chemotherapy cancer survivors, through intra-testicular transplantation of autologous, purified, bone marrow-derived CD34+/CD133+ stem cells. We isolated CD34+ and CD133+ cells from human bone marrow using the clinical-grade CliniMACSPLUS® Cell Purification System. CD34+/CD133+ cell populations were directly separated from MNCs collected from the bone marrow. Flow cytometry analyses for purified cell populations showed 94.5 (+3.2) % purities. CD34+/CD133+ purified populations were then injected intra-testicularly in patients on the same day of the procedure. Patients were then followed up for up to 5 years post-transplantation. No complications were reported in any patient in this study. Nine out of twenty seven patients (33%) showed pathological changes. Some cases developed spermatids in the testes (7%), while others developed fully mature spermatozoa (11%). Spermatocytes and sperms appeared in the seminal fluid in a few other cases after SCT (26%). Long term results yielded 6 natural pregnancies, 2 live births, and 1 successful IVF out of 3 (1/3) done for three couples. The advantage of using autologous adult BMSCs is in the generation of the patients' own biological offspring. Additionally these cells differentiate in vivo when placed in the gonad environment to spermatocytes, spermatids, and even mature spermatozoa. All together, this procedure minimizes the risk of genetic instability, since no propagation takes place in vitro (culture), avoids manipulation and epigenetic alteration, stabilizes the properties of the mature spermatozoa and produces a healthy offspring after transplantation. The introduction of purified, uncultured, un-manipulated, CD34+/CD133+ BMSCs into the testicles of infertile patients is a promising technique that may carry some hope for male infertility patients. Citation Format: Adeeb M. AlZoubi. Intra-testicular transplantation of purified autologous stem cells for treatment of chemotherapy-induced male infertility. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3038. doi:10.1158/1538-7445.AM2014-3038