Male hypogonadism is a condition that diminishes testosterone amounts in approximately 30% of older men, but currently available remedies can produce serious side effects. In a study published December twenty two in Stem Cell Reports , scientists developed an alternative approach involving the direct conversion of grownup skin cells into functional testosterone-producing cells. When transplanted into male rodents with hypogonadism, these so-called Leydig-like cells survived and restored normal testosterone levels.
“Our study is the first in order to report a method for generating Leydig cells by means of immediate cell reprogramming, ” says senior study co-author Yadong Huang of Jinan University. “This alternative source of Leydig cells will be of great significance for basic research and provides the particular attractive prospect of clinical application in the field of regenerative medication. ”
Male hypogonadism is characterized by signs and symptoms such as mood disturbances, sexual dysfunction, decreased muscle mass plus strength, and decreased bone mineral density. One principal cause is the dysfunction of testosterone-producing Leydig cells within the testes. Testosterone replacement therapy can alleviate some signs and symptoms resulting from Leydig cell failure, but it may also increase the danger of prostate and cardiovascular complications, such as the formation associated with blood clots.
Leydig cell transplantation is actually a promising alternative to hormone replacement therapy, providing physiological designs of hormone for a longer period of time. However , stem cell-based approaches are costly, time-consuming, and limited by ethical issues and the risk of tumor formation. Huang and co-senior study author Zhijian Su of Jinan University reasoned that the direct conversion of adult skin cells directly into Leydig cells would be a faster, safer regenerative medicine method.
To test this idea, the researchers tested 11 transcription factors that could affect the ability of Leydig cells to produce testosterone. Using lentiviral vectors to drive the expression of three of these transcriptional factors, Dmrt1, Gata4, and Nr5a1, they were able to directly reprogram computer mouse skin cells into functional Leydig-like cells, which demonstrated normal gene activity and were capable of producing testo-sterone. When transplanted into the testes of rats or rodents with hypogonadism, these cells survived and restored regular testosterone levels.
According to the authors, future research should aim to improve the efficiency of the approach to generate the pure population of cells that closely mimic mature Leydig cells. For their own part, the researchers are usually examining in more detail the mechanisms underlying the immediate conversion of skin cells into Leydig-like cells. To help make the findings more relevant to patients, they are also examining direct mobile conversion strategies using small molecules and other non-viral strategies. “In the end, we are hopeful that this research will pave the way for clinical trials testing a novel regenerative medicine approach to treat androgen deficiency in men, inch Su says.
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