It sounds like science fiction: collecting blood cells from a person, engineering them to eventually develop into immature sperm, and then incubating them in a small sac grown in a mouse’s kidney.

The quest to have babies with lab-grown eggs and sperm

But it is not. Today, a team of researchers reported in the journal cell stem cell¹ who has successfully carried out the procedure, whose ultimate goal is to produce mature human sperm in the laboratory.

For now, that goal remains elusive. Cells grown in the laboratory stopped developing at an immature stage. Many hurdles need to be overcome to create mature sperm in the lab, says Eoin Whelan, a reproductive biologist at the University of Pennsylvania in Philadelphia, a member of the research team. But the latest feat is a step in the right direction.

Meanwhile, the procedure could be used to study the early stages of human sperm development and look for the reasons behind male infertility. About 40% of male infertility cases have no known cause. “We’re approaching this from a basic science perspective,” Whelan says. “We are very far from clinical application.”

An elusive target

Some of the potential clinical applications are controversial, particularly the idea of ​​using lab-grown sperm or eggs to produce babies. Although some researchers hope that this approach can be used to treat specific cases of infertility, the practice also raises ethical concerns. One is that the technique could facilitate the genetic modification of reproductive cells to produce “designer babies.”

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So far, a handful of researchers have been able to produce mouse eggs and sperm from mouse skin cells. These cells are genetically reprogrammed to become induced pluripotent stem (iPS) cells: “young” cells that act like those of embryos and can be chemically or genetically induced to become completely different cells, such as sperm. One team even used this method to generate offspring from two male mice.².

But researchers have not been able to translate these successes in mice to humans or other primates because of differences in the way the species develop. Human fetal development is also difficult to study, so researchers trying to understand and recapitulate the early days of sperm and egg development are left groping in the dark. “In humans, the work is far behind,” says Kotaro Sasaki, a developmental biologist also at the University of Pennsylvania.

Step by step

Sasaki and his colleagues previously determined how to convert human iPS cells into those that resemble the early embryonic cells that will eventually give rise to eggs and sperm.³. The researchers then mixed those immature cells with non-reproductive cells found in the testes of developing mice.⁴. Non-reproductive mouse cells can provide the protection and nutrients necessary to support sperm development.

This allowed Sasaki and his colleagues to tiptoe closer to growing mature sperm, but the cells did not progress beyond the initial stage of sperm development found in human fetuses.

Now, Sasaki, Whelan and their colleagues have taken the process further by transplanting their mixture of cells into live mice, in a region of the kidney known to be well suited to supporting transplanted tissues.

Once in that bag, the transplanted cells self-organized into tubular structures similar to those of the testicles, where sperm are produced. Six months after the transplant, the human cells had developed into spermatogonia, a type of cell that can eventually give rise to mature sperm.