Human stem cells developed into sperm cell precursors in tissue grown on a mouse kidney
Human stem cells developed into sperm cell precursors in tissue grown on a mouse kidney
A team at the University of Pennsylvania returned human cells to an early developmental state, directed them toward the germline, and placed them in engineered testicular tissue. After six months, the cells had become spermatogonia, the precursors of mature sperm cells.
In a study published in Cell Stem Cell, the researchers began with induced pluripotent stem cells, or iPS cells. These cells are produced by reprogramming ordinary cells, such as blood or skin cells. They can then be placed on an early developmental trajectory and directed toward primordial germ cells, the common precursors of eggs and sperm.
Chemical signals alone were not enough for the next stage. The team combined the human germ cell precursors with supporting cells from developing mouse testes. They transplanted the resulting construct beneath the kidney capsule of an immunodeficient mouse. There, it acquired a blood supply and organized itself into tubules resembling those in which germ cells develop within the testis.
After six months, the human cells had developed into spermatogonia. This is still an early stage. A spermatogonium divides and produces cells that later undergo meiosis, a specialized form of cell division that reduces the chromosome set, before becoming mature sperm cells. The authors confirmed that the cells were human and examined their protein markers and gene activity at single-cell resolution. In an earlier version of the study, some cells also reached an early stage of meiosis.
The tissue environment was essential. The team had previously produced early germ cells in a Petri dish, but the engineered tissue lost its organization after approximately 80 days. On the mouse kidney, it survived longer, developed blood vessels, and carried the human cells further through their developmental program. A cell needs instructions, but prolonged development also requires a functioning piece of tissue.
This work extends an existing approach to fertility preservation. In May, testicular tissue frozen before puberty produced sperm after being transplanted back into the patient. In that case, physicians preserved the patient’s own germline. The new study starts with reprogrammed cells and builds a temporary tissue environment for them.
There is still a long way to go before this method produces mature human sperm. The current system depends on mouse cells and transplantation into a mouse, so its most immediate use is to study early development and the causes of male infertility. Even so, it already makes it possible to investigate questions that were previously difficult to address because human tissue was unavailable, including which signals keep a germ cell on the correct developmental path and where that program breaks down.