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This review evaluates the state of the art in terms of challenges and strategies used to restore fertility with spermatogonial stem cells retrieved from prepubertal boys affected by cancer. Although these boys do not yet produce spermatozoa, the only option to preserve their fertility is cryopreservation of spermatogonial stem cells in the form of testicular cell suspensions or whole tissue pieces. Different techniques have been described to achieve completion of spermatogenesis from human, spermatogonial stem cells but none is yet ready for clinical application. A crucial point to address is gaining a full understanding of spermatogonial stem cell niche pathophysiology, where germ cells undergo proliferation and differentiation. Various fertility restoration approaches will be presented depending on the presence of an intact niche, dissociated niche, or reconstituted niche.Testicular organoids open the way to providing further insights into the niche. They can recreate the three-dimensional architecture of the testicular microenvironment in vitro, allowing a large number of applications, from physiology to drug toxicity investigations.In addition to the full elucidation of the niche microenvironment, achieving fertility restoration from cryopreserved human spermatogonial stem cells implies overcoming other important challenges. Testicular organoids might prove to be essential tools to progress in this field.