In Vitro Systems for Spermatogonial Stem Cell Development
Summary
The cultivation of spermatogonial stem cells (SSCs) outside the testis has evolved markedly, driven by the need to understand male germ cell biology and to develop fertility preservation strategies. Early two-dimensional (2D) cultures provided proof of concept for SSC maintenance and proliferation, yet lacked the complex cell–matrix interactions of the native testis. The introduction of three-dimensional (3D) culture systems using natural and synthetic scaffolds, hydrogels or decellularised matrices has enabled the self-organisation of SSCs with supporting somatic cells into structures that approximate seminiferous tubules. Advances in biofabrication, including microfluidic bioreactors and hanging-drop platforms, have further refined nutrient exchange and paracrine signalling, fostering long-term survival and differentiation. Organoid technologies, in which SSCs reaggregate with Sertoli and Leydig cells, now permit partial progression through meiosis, while organotypic culture of testicular fragments retains native architecture for extended periods. These in vitro systems have facilitated studies of germ-cell niche factors, hormonal regulation, toxicology screening and genome editing, and hold promise for generating haploid gametes for clinical and research applications. Ongoing challenges include achieving complete spermatogenesis in human models, reproducing the intricate spatial gradients of growth factors, and scaling up for translational use.
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In Vitro Systems for Spermatogonial Stem Cell Development publication trend
The graph below shows the total number of articles in in vitro systems for spermatogonial stem cell development across all publications each year (not limited to Nature Index journals).
Technical terms
Spermatogonial stem cell (SSC): An adult stem cell in the testis responsible for self-renewal and generation of differentiating germ cells leading to sperm formation.
Three-dimensional (3D) culture system: A cell culture approach using scaffolds or hydrogels to recreate tissue-like spatial architecture and cell–matrix interactions.
Organoid: A self-organised multicellular structure grown in vitro that recapitulates key aspects of organ architecture and function.
Extracellular matrix (ECM): A complex network of proteins and polysaccharides surrounding cells, providing structural support and biochemical cues.
In vitro spermatogenesis (IVS): The laboratory process by which SSCs are induced to undergo proliferation, meiosis and differentiation into sperm-like cells.
References
- Advances of three-dimensional (3D) culture systems for in vitro spermatogenesis. Stem Cell Research & Therapy (2023).
- Generation of Organized Porcine Testicular Organoids in Solubilized Hydrogels from Decellularized Extracellular Matrix. International Journal of Molecular Sciences (2019).
- Organ culture of seminiferous tubules using a modified soft agar culture system. Stem Cell Research & Therapy (2018).
- Establishment and Characterization of Testis Organoids with Proliferation and Differentiation of Spermatogonial Stem Cells into Spermatocytes and Spermatids. Cells (2024).
- Spermatogonial Stem Cells for In Vitro Spermatogenesis and In Vivo Restoration of Fertility. Cells (2020).
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