Scientists have succeeded in reprogramming stem cells into sperm progenitor cells

Scientists have long been trying to produce sperm and eggs in the lab. This would not only allow them to better understand one of the most fundamental biological processes, but also, potentially, to develop new ways to help infertile couples. Using embryonic stem cells, which are theoretically capable of transforming into any type of cell, several research groups have made some progress in recent years, but no one has succeeded in producing viable sex cells.

Scientists at Kyoto University have recently found a way to reprogram mouse embryonic stem cells into sperm precursor cells and, using the resulting sperm, produce normal mice. Their research could eventually lead to new treatments for male infertility. However, according to the team's leader, biologist Mitinori Saitou, this would require solving several "very difficult" technical and ethical issues.

As is known, sperm and eggs develop from primary, or primordial, germ cells (PGCs). Primordial germ cells are formed in the early stages of embryogenesis from a mass of cells called the epiblast. Several years ago, scientists learned to take epiblast cells from a mouse embryo and transform them into epiblast stem cells, which are capable of long-term regeneration in the laboratory. Researchers hoped that such cells could be used to obtain primordial germ cells and, ultimately, sperm and eggs. But despite years of experimentation, no one has yet succeeded. Japanese scientists have concluded that when epiblast stem cells obtained in the laboratory acquire the ability to grow for a long time, they lose the ability to form germ cells.

So, changing their approach, they decided to cultivate mouse embryonic stem cells in a cocktail of growth factors to obtain cells similar to epiblast cells, which live only a few days. The researchers found that 2-day-old cells could be used to obtain cells similar to primordial germ cells. When injected into the testicles of mice that were unable to produce their own sperm, these primordial stem cells matured into sperm, which successfully fertilized eggs in vitro experiments. The scientists implanted the resulting embryos into surrogate mothers, who produced normal offspring. The mice born in this unusual way grew up to be fertile females and males, and later also produced healthy offspring. In a similar way, fertile offspring can be obtained from induced pluripotent stem cells (iPSCs) differentiated from adult skin cells.

"All I can say is wow! This is a breakthrough!" said Orly Lacham-Kaplan, a reproductive biologist at Monash University in Australia.

The work provides evidence "that primordial germ cells derived from embryonic stem cells can develop into functional germ cells," says Amander Clark, a biologist at the University of California, Los Angeles, who calls the Japanese researchers' work "a decisive breakthrough in our understanding of how germ cells develop."

There are still many hurdles to overcome, Saito says. They would like to learn how to carry out the entire process of producing mature sperm directly in the lab, rather than injecting primordial-like sex cells into the testes to mature. Another goal is to produce eggs in vitro, not only to understand the process itself, but also to eventually try to help infertile women. But first, to transfer their results to the clinic, they need to establish whether the “recipe” they have found, which has proven so successful for mouse stem cells, will work in human cells.

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