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4. Safety of artificial gametes Finally, the long-term safety of the obtained artificial gametes will be a critical issue to assess the quality and applicability of derived artificial gametes into the clinical practice. Observational and biochemical tests can be performed to demostrate the safety of artificial sperm or eggs, but these assays are insufficient to judge whether the cells would support normal development in humans upon fertilization until the adult life. The most robust and stringent studies reporting human PCGs generated in vitro have shown that these cells present normal germ cell genetic and epigenetic profiles and are able to colonize [14] and proliferate when xenotransplanted into mice testes [15,49]. However, some other works have reported incomplete imprinting of the generated germ-like cells [53]. These findings highlight the need for more consistent research that should be focused to the following main directions: (1) tumorigenicity of the cells as in vitro culture of stem cells for long periods as well as reprogramming of patient-specific somatic cells to hiPSCs have been shown to constitute risks factors for accumulation of chromosomal aneuploidies [110,111]; (2) immunogenicity of in vitro generated gametes, which remains a challenge for their use as potential progenitors to be transplanted into the host as they could produce immunological rejection problems even if they are used in autologous therapy, as it has been reported for some hiPSCs cell lines [112]; (3) the future use of artificial gametes in regenerative medicine programs would require the obtention of therapeutic grade sperm and eggs JNK inhibitor ic50 attending to strict production conditions that guarantee that these cells do not present additional risks acquired during their manipulation. Conclusion Generation of artificial gametes is a great promise for all those couples that, for many different reasons, currently need to go to gamete donation for fulfilling their wish to have children but would prefer to have genetically related offspring due to ethical, social or emotional reasons. Also, the successful generation of artificial gametes will help to understand the complex biological process of gametogenesis in humans, leading to the improvement in the knowledge and potential treatments of many disorders related to infertility and those diseases that are genetically transmitted to the progeny. Despite the great interest that this field has arisen in the last years, there is still a long way to go until artificial germ cells will be used in the clinical practice. First, from the technological point of view, the accumulated knowlegde learnt from the mouse model needs to be translated to humans considering the important differences between both species.