Sperm stem cells are normally found in the testes, where they divide to help provide a continuous supply of sperm. While sperm stem cells have two sets of chromosomes, mature sperm capable of fertilising eggs have only one set.

In a first step towards creating artificial sperm cells, researchers have turned human bone marrow tissue into primitive sperm cells.

If these precursor cells can be coaxed into becoming fully functioning sperm cells, the technique could allow infertile men to father their own children, and even allow women to produce their own sperm. But experts caution that provoking the sperm precursors to fully mature presents a serious challenge.

In July 2006, biologist Karim Nayernia at the University of Newcastle-upon-Tyne in the UK, and colleagues reported they had successfully converted stem cells from mouse embryos into functioning sperm that could fertilise mouse eggs and produce live offspring.

Nayernia says trying this approach in humans would spark controversy as it would involve creating embryonic clones of infertile men: “If we used this method in the clinic, it would raise ethical concerns.” He believes his latest advance, which instead used stem cells taken from bone marrow, would present fewer ethical problems.


Continuous supply

Nayernia’s team obtained the bone marrow stem cells, called mesenchymal stem cells, from four adult men who were about to undergo bone marrow transplants. The researchers mixed these cells with proteins that promote cell growth and vitamin A, which appears to play an important role in sperm development. This mixture converted the cells into sperm stem cells, called spermatogonium cells.

Sperm stem cells are normally found in the testes, where they divide to help provide a continuous supply of sperm (see diagram, right). While sperm stem cells have two sets of chromosomes, mature sperm capable of fertilising eggs have only one set.

Nayernia says his ongoing experiments have suggested that sperm cells derived from the bone stem cells of mice can undergo the first two of three divisions necessary to become mature sperm. He says that his team will work to achieve all the necessary divisions in mice before trying similar manipulations with human cells.

The acid test

Experts caution that turning sperm stem cells derived from bone marrow into functioning sperm would be no small feat. “Before we get too excited about this being a new form of infertility treatment, these cells cannot as yet be made into functioning sperm, so we have no idea if they can pass ‘the acid test’ – the ability to fertilise female eggs as is achieved with donor sperm in IVF treatment,” says Malcolm Alison of the London School of Medicine and Dentistry in the UK.

Stem cell biologist Harry Moore at the University of Sheffield in the UK worries that sperm created from bone stem cells could have undetectable abnormalities that could cause disease in offspring. “Unfortunately, these stem cell manipulations can lead to permanent genetic changes which would make them unsafe to use especially as a potential sperm or egg,” he says.

Nevertheless, Nayernia remains optimistic about manipulating stem cells to treat infertility, and says a positive outcome could help many men, including those whose sperm stem cells have been destroyed by potent anti-cancer drugs.

Female sperm

Nayernia hopes that one day it might be possible to inject the sperm stem cells directly into the testes of human patients, so that these men can conceive naturally as opposed to using IVF.

And women may be able to use the technique to produce sperm, allowing lesbian couples to have their own biological daughters. Nayernia says that researchers have produced the same early-stage sperm cells in mice from bone marrow cells taken from female mice.

“It should be perfectly possible for fully functional mature sperm cells to be made from these female-derived cells too,” he told New Scientist.

Reference: Gamete Biology: Emerging Frontiers on Fertility and Contraceptive Development (SRF 63, p 69, 2007)