Biofactory of testosterone
Subcutaneous autotransplantation of Leydig stem cells may be effective in the treatment of hypogonadism
Specialists from the University of Miami have tested a new method of treating testosterone deficiency in mice. They subcutaneously injected rodents with their own Leydig stem cells, which produce male sex hormones – androgens (testosterone, dihydrotestosterone) together with Sertoli cells, which, along with other cells of the hemato-testicular barrier, protect spermatozoa from their own immune system, and myoid cells, which are part of the seminal tubule shell. The results showed that the level of testosterone in the recipients' blood increased without changes in the level of luteinizing and follicle-stimulating hormones.
The work was published in the scientific journal Stem Cells Translational Medicine (Arora et al., Subcutaneous Leydig Stem Cell Autograft: A Promising Strategy to Increase Serum Testosterone).
Testosterone in men is produced mainly in Leydig cells, and their dysfunction can lead to a deficiency of the sex hormone (hypogonadism). The current standard of treatment for hypogonadism is lifelong testosterone replacement therapy. However, it is associated with the development of a number of side effects. In particular, due to the inclusion of a negative feedback mechanism along the hypothalamic-pituitary-gonadal axis, the production of luteinizing and follicle-stimulating hormones (LH and FSH) decreases in patients, which leads to the development of infertility. Other negative effects of therapy can be gynecomastia, polycythemia, hypertension, acne and hair loss. With long-term use of sex hormone, the risks of myocardial infarction, strokes and prostate cancer increase.
Currently, scientists are investigating various ways to increase testosterone levels in the male body without affecting the hypothalamic-pituitary-gonadal axis and preserving the fertility of patients.
Recent studies on stem cell transplantation into testicles have shown good results. However, this technique is of little use in practice, since it requires repeated invasive interventions to plant material in the testicles.
American scientists have studied whether subcutaneous autotransplantation of Leydig stem cells can help in the treatment of testosterone deficiency.
Leydig stem cells were isolated from the testicles of 12-week-old mice, then subcutaneously injected into them after castration in combination with Sertoli cells and myoid cells (the authors found that stem cells themselves are not capable of self-renewal and differentiation, but in combination with Sertoli and myoid cells are converted into mature Leydig cells).
According to the results of the studies, the recipient mice showed an increase in the level of testosterone in the blood serum while maintaining the level of luteinizing hormone. Experts found that testosterone production in transplanted autografts was regulated by the hedgehog signaling pathway (HH). The introduction of Desert HH (DHH) agonists and DHH antagonists led to an increase and decrease in testosterone levels, respectively.
This study was the first to show that autotransplantation of Leydig stem cells in combination with Sertoli cells and myoid cells leads to an increase in serum testosterone levels without affecting LH and FSH levels. Further studies are expected to be conducted on mice with normal levels of sex hormone.
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