When Regenerative Medicine Faces the Challenges of Reproductive Medicine: A Review Study on Recent Advances in the Strategies for Derivation of Gametes from Stem Cells

Abstract

The murine model has allowed for the replication of all developmental stages of the mammalian germline in vitro, from embryonic stem cells to epiblast cells, primordial germ cells, and finally into functional haploid gametes. However, because of interspecies differences between mice and humans, these results are yet to be replicated in our species. Reports on the use of stem cells as a source of gametes, retrieved from public scientific databases, were analysed and classified according to the animal model used, the stem cell source and type, the differentiation strategy, and its potential application. This review offers a comprehensive compilation of recent publications of key events in the derivation of germ cells and gametogenesis in vitro, in both mice and human models. Additionally, studies intending to replicate the different stages in human cells in vitro, in order to obtain cells with a phenotype akin to functional human gametes, are also depicted. The authors present options for deriving gametes from stem cells in vitro and different reproductive options for specific groups of patients. Lastly, the potential applications of in vitro human gametogenesis are evaluated as well as the main limitations of the techniques employed. Even though it appears that we are far from being able to obtain gametes from pluripotent stem cells in vitro as a viable reproductive option, its current academic and clinical implications are extremely promising.