U.S. scientists succeeded in growing stem cells made from human blood cells into sperm. In particular, they matured them together with testicular cells, bringing the environment closer to the human body. Although the cells are still at a stage before sperm, the work is expected to be used to study the early stages of human sperm development and to identify causes of male infertility. About 40% of male infertility cases remain unexplained.
A team led by Kotaro Sasaki, a professor at the University of Pennsylvania Perelman School of Medicine, said on the 10th (local time) in the journal Cell Stem Cell that it "differentiated human induced pluripotent stem cells (iPS cells) made from human blood cells into immature sperm and cultured them in artificial testicular tissue transplanted into a mouse kidney."
◇ Transplanting artificial testes into mouse kidneys
iPS cells are created by introducing specific genes or proteins into already fully grown somatic cells, such as skin or blood cells, to revert them to the embryonic stem cell state of early development. Embryonic stem cells in a fertilized egg, where a sperm and egg meet, grow into all the cells and tissues of the human body.
In 2015, when Sasaki was a postdoctoral researcher at Kyoto University in Japan, he succeeded in converting human iPS cells into a form similar to early embryonic cells that differentiate into sperm and eggs. Then in 2020 at the University of Pennsylvania, he devised a method to culture human immature sperm cells mixed with mouse testicular cells. That way, as in the human body, testicular cells protect the immature sperm and provide nutrients. However, the work did not move beyond the earliest stages of sperm development.
The researchers advanced the work a step further this time. They mixed pre-sperm cells derived from iPS cells with testicular cells and transplanted them into mouse kidneys. The cells then self-organized into a tubular structure similar to where sperm are produced in the testes. Six months after transplantation, the human cells developed into spermatogonia. Spermatogonia undergo meiosis to become tailed sperm. The team also produced spermatogonia in macaque monkeys using the same method.
This study still has limitations. The spermatogonia did not differentiate into mature sperm. The same was true for monkey cells. Sasaki suggested that a likely reason is that the human spermatogonia grew with help from mouse kidney cells, which are a different species. He noted that for sperm to grow, they need signals not only from surrounding somatic cells but also hormones from distant organs, and problems can arise if those signals come from a mouse.
The team plans to further develop the research to determine whether human spermatogonia made from iPS cells can perform actual sperm functions. However, most countries strictly limit research using stem cells, eggs, and sperm. To avoid such legal restrictions and ethical controversies, Sasaki plans to continue the same line of research using macaque monkeys.
◇ Private corporations are also active in sperm and egg research
Research to create germ cells from iPS cells has advanced rapidly. In 2011, a Kyoto University team made iPS cells from skin cells and grew them into sperm. In 2012, they produced eggs the same way. Females born after fertilization with the sperm later gave birth to healthy offspring. In 2023, a Kyushu University team also opened a path for a father to have a baby without a mother. They differentiated iPS cells from male mice into eggs, fertilized them with normal sperm, and produced offspring.
Studies using human iPS cells have also made progress. In 2024, a Kyoto University team differentiated human iPS cells made from blood cells into pre-sperm and pre-egg stages. But unlike in mice, they did not succeed in fertilization and birth. The current team also did not produce fully formed sperm. Even so, by culturing not in a culture dish as in previous studies but in a kind of artificial testis, they took research on germ cell differentiation and culture a step further, according to assessments.
Private corporations are also working to produce eggs and sperm in the lab. Last month, Conception, a biotech corporation in Berkeley, California, said it cultured immature human eggs in the lab using stem cells. In May, Paterna Biosciences in Salt Lake City, Utah, said it cultured mature sperm. Paterna used immature sperm cells collected from the testis instead of iPS cells.
References
Cell Stem Cell (2026), DOI: https://doi.org/10.1016/j.stem.2026.06.001
Nature (2024), DOI: https://doi.org/10.1038/s41586-024-07526-6
Nature (2023), DOI: https://doi.org/10.1038/s41586-023-05834-x
Nature Communications (2020), DOI: https://doi.org/10.1038/s41467-020-19350-3
Science (2012), DOI: https://doi.org/10.1126/science.338.6103.24-b
Cell (2011), DOI: https://doi.org/10.1016/j.cell.2011.06.052