Cell therapy against hypogonadism
Jinan University researchers have developed and successfully tested on male rodents an alternative approach to the treatment of hypogonadism, which consists in transplanting testosterone-producing cells derived from skin cells into the seminal glands using the direct conversion method.
Male hypogonadism is a condition that leads to a decrease in testosterone levels in about 30% of older men. It is characterized by mood disorders, impaired sexual function, a decrease in muscle mass and strength, and a decrease in bone mineral density. The main cause of the development of the disease is a violation of the functions of the Leydig cells producing the male sex hormone testosterone, located in the seminal glands. Hormone replacement therapy can alleviate a number of symptoms of hypogonadism, but it can increase the risk of complications from the prostate and cardiovascular system, such as the formation of blood clots.
Leydig cell transplantation is a promising alternative to hormone replacement therapy, potentially capable of maintaining physiological testosterone levels for a long time. However, cell-based therapeutic approaches require large financial and time costs, and their use is severely limited by ethical issues, as well as the risk of developing tumors. The authors suggested that the direct conversion of adult skin cells into Leydig cells could become a faster and safer approach of regenerative medicine.
To test their idea, they screened 11 transcription factors that potentially affect the ability of Leydig cells to produce testosterone. With the help of lentiviral vectors providing expression of three of these transcription factors – Dmrt1, Gata4 and Nr5a1 – they carried out direct reprogramming of mouse skin cells into functional cells-analogues of Leydig cells having normal gene activity and capable of producing testosterone. When transplanted into the seminal glands of male mice and rats with hypogonadism, these cells took root and restored normal testosterone levels in the body.
In the image, fibroblasts expressing green fluorescent protein (yellow arrows, left) and induced Leydig cell analogues (green cells on the right) migrate to the interstitial regions of the seminal tubules after transplantation. The latter express all the enzymes necessary for the synthesis of steroid hormones and produce testosterone under the action of luteinizing hormone.
The authors note that the goal of future research is to increase the effectiveness of the approach aimed at creating a pure population of cells that are analogues of Leydig cells. Currently, they are engaged in a more detailed study of the mechanisms that ensure the direct conversion of skin cells into testosterone-producing cells. In addition, they are searching for small molecules that could provide such a conversion without the use of viral vectors.
Article by Yang et al. Direct reprogramming of mouse fibroblasts toward Leydig-like cells by defined factors published in the journal Stem Cell Reports.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on EurekAlert materials!: A stem cell strategy for boosting testosterone levels tested in rodents.
28.12.2016