In‐vitro spermatogenesis through testis modelling: Toward the generation of testicular organoids

BACKGROUND: The testicular organoid concept has recently been introduced in tissue engineering to refer to testicular cell organizations modeling testicular architecture and function. The testicular organoid approach gives control over which and how cells reaggregate, which is not possible in organotypic cultures, thereby extending the applicability of in‐vitro spermatogenesis (IVS) systems. However, it remains unclear which culture method and medium allow reassociation of testicular cells into a functional testicular surrogate in‐vitro. OBJECTIVE: The aim of this paper is to review the different strategies that have been used in an attempt to create testicular organoids and generate spermatozoa. We want to provide an up‐to‐date list on culture methodologies and media compositions that have been used and determine their role in regulating tubulogenesis and differentiation of testicular cells. SEARCH METHOD: A literature search was conducted in PubMed, Web of Science, and Scopus to select studies reporting the reorganization of testicular cell suspensions in‐vitro, using the keywords: three‐dimensional culture, in‐vitro spermatogenesis, testicular organoid, testicular scaffold, and tubulogenesis. Papers published before the August 1, 2019, were selected. OUTCOME: Only a limited number of studies have concentrated on recreating the testicular architecture in‐vitro. While some advances have been made in the testicular organoid research in terms of cellular reorganization, none of the described culture systems is adequate for the reproduction of both the testicular architecture and IVS. CONCLUSION: Further improvements in culture methodology and medium composition have to be made before being able to provide both testicular tubulogenesis and spermatogenesis in‐vitro.