Background: The endangered koala presents an urgent case for reproductive biobanking, yet spermatogonial stem cell (SSC)-based strategies, increasingly applied in human fertility preservation, remain unexplored as a conservation tool. Here, we present the first systematic evaluation of testicular cell isolation, SSC enrichment and short-term culture in the koala, directly testing whether SSC biobanking protocols built for eutherian mammals translate to a marsupial.
Methods: To encourage SSC enrichment, testicular cell suspensions from n=9 koalas were subjected to Percoll density-gradient centrifugation, differential plating, and magnetic-activated cell sorting (MACS) using ITGA6. Fractions were assessed by qPCR, immunocytochemistry using DDX4, PLZF, STRA8, SOX9 and Vimentin antibodies, and short-term culture recovery. Data were analysed using paired t-tests, Kruskal–Wallis/Dunn or ANOVA/Tukey tests, as appropriate.
Results: Unselected suspensions contained DDX4+ germ cells, including PLZF+ SSCs (<11% of total cell population) and STRA8+ differentiating spermatogonia, alongside SOX9+ and Vimentin+ somatic cells. In contrast to eutherian mammals, Percoll centrifugation did not enrich for koala spermatogonia, indicating species-specific buoyant density. Differential plating depleted STRA8+ differentiating spermatogonia (p=0.0249), however only modestly enriched PLZF+ SSCs (1.6-fold, p=0.0757). Unexpectedly, ITGA6-MACS failed to enrich PLZF+ SSCs in the selected population, but rather depleted Vimentin+ stromal cells (p=0.0372), creating a 2.4-fold enrichment in PLZF+ SSCs in the flow-through (p=0.0400). qPCR analysis mirrored these findings, with a 1.8-fold increase in Plzf transcript abundance in the flow-through relative to the selected fraction, with similar trends for additional SSC markers, Gfra1 and Uchl1. Promisingly, when placed in culture, flow-through cells displayed characteristic spermatogonial morphology and superior short-term recovery.
Conclusion: This study establishes the first platform for koala SSC isolation and culture, revealing that enrichment strategies routinely used in eutherian mammals do not translate to marsupials. By identifying the flow-through as an unexpectedly SSC-enriched fraction, this work lays essential groundwork for koala-specific biobanking and future genetic rescue efforts.Â