P055
Generation of testicular organoids from Klinefelter Syndrome patient testis
M Martin-Inaraja(1,2,4) I Romayor(1,2,3,4) A Sáez de Cámara(1,2,4) S Santos(1,2,4) C Rodríguez(1,2,4) J P Alves-Lopes(5) J B Stukenborg(5) C Eguizabal(1,2,4)
1:Cell Therapy, Stem Cells and Tissues Group, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain; 2:Research Unit, Basque Center for Blood Transfusion and Human Tissues, Osakidetza, Galdakao, Spain; 3:Cell Biology and Histology Department, University of the Basque Country (UPV/EHU), Leioa, Spain; 4:Red Española de Terapias Avanzadas (TERAV), Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS RD21/0017/0024), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; 5:NORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Solna, 17164 Stockholm, Sweden
Klinefelter Syndrome (KS) is an aneuploid genetic condition where a male has an additional copy of the X chromosome, 47,XXY karyotype. Due to fibrotic degeneration of the testis, these patients suffer infertility in the future. The pathogenic mechanism is not well known, and spermatogonia stem cells (SSCs) are scarce in these patients. Therefore, an in vitro system allowing efficient expansion of SSCs is required. A strategy to address the improvement of in vitro expansion of SSCs is through the generation of testicular organoids. For that, we generated induced pluripotent stem cells (iPSC) from KS patients, with the aim to differentiate those iPSCs towards testicular cells and to create testicular organoids. . These cells maintain the pluripotency stage and are capable to differentiate into endoderm, mesoderm and ectoderm cell layers. This demonstrates that the derived iPSC has characteristics of pluripotent stem cells. In addition, we have seen that frozen testicular biopsies from KS patients can form testicular organoid and maintain germ cells and Sertoli cells in culture for 14 days. If successfully differentiated into germ cells and testicular somatic cells, our iPSC lines could be the first step to provide a unique in vitro platform to study the molecular mechanisms underlying pathophysiology of the testes in KS patients.