A potential new treatment for male infertility is being tested by researchers at the University of Georgia (UGA) Emory University School of Medicine and the University of Pittsburgh. They will be reprogramming skin cells into sperm-generating cells, which can be transplanted into infertile males to restore sperm production.
At puberty, spermatagonial stem cells kick into action and start producing sperm. These spermatagonial stem cells are responsible for maintaining a male’s ability to keep producing sperm throughout life. However, if the population of stem cells is wiped out, or the cells are otherwise damaged, males will be infertile. There are many possible causes of infertility, such as exposure to certain environmental factors or treatments for some diseases. In the case of the latter, radiation therapy and chemotherapy can have that effect and can render males infertile. Infertility is common in children who have successfully completed cancer therapy.
The technique of reprogramming adult skin cells into pluripotent stem cells was devised by the Japanese scientist Shinya Yamanaka, with his work earning him a Nobel Prize in 2012. The technique involves harvesting skin cells from a patient and converting them into induced pluripotent stem cells (IPSCs) – stem cells that resemble embryonic stem cells. IPSCs can, under the right conditions, develop into any cell type in the body.
Several methods can be used to reprogram the stem cells, such as introducing the necessary genes into the cells – termed Yamanaka factors – or activating some of the genes already present in the cell using a modified version of CRISPR-Cas9. In the case of the latter, CRISPR is used to activate genes without cutting the DNA.
In this study the researchers will be using skin cells harvested from Rhesus macaque monkeys and will reprogram the cells to convert them to IPSCs, which will then be differentiated into spermatogonial stem cells. Those cells will then be introduced into the testes. If the technique is successful, the cells should be capable of producing viable sperm and the technique could be applied to humans and would involve a one-time treatment.
The researchers have recently been awarded a grant of $2.9 million from the National Institutes of Health for the research. The purpose of the study is to test the safety of the technique and determine whether sperm production can be restored in sterile testes. The same technique could be used for female cancer survivors to restore egg production. Since the skin cells are harvested from the patient who will receive the treatment, the resultant sperm or eggs will contain the patient’s DNA and the immune systems should not reject the cells.
The study is being led by Charles Easley, assistant professor at the UGA College of Public Health and member of the Regenerative Bioscience Canter at UGA. If the technique works, the next stage will be clinical trials to determine whether the sperm can go on to fertilize eggs and produce viable human embryos.