Breakthrough in testosterone-producing cells could lead to treatment for ‘low T’

[madman]

Breakthrough in testosterone-producing cells could lead to treatment for ‘low T’


Low testosterone can affect men’s mood, sex life and health. USC scientists say they’ve hit upon a potential new solution.

 

[madman]

Vassilios Papadopoulos, right, with researcher Lu Li. His team has found a way to grow testosterone-producing cells in a lab for the first time, using a combination of stem cells, human collagen, nutrients and other ingredients.

 

[madman]

Human collagen helps cells produce testosterone

Previous attempts to cultivate human Leydig cells have come up short. In one study, the lab-grown cells produced cortisol, not testosterone, Papadopoulos said. Other experiments have involved stem cells from bone marrow or the umbilical cord; harvesting these cells is more labor-intensive and they do not multiply as well in the lab.

In Papadopoulos’s experiment reported today, researchers started with stem cells called human-induced pluripotent stem cells, which come from human skin or blood and can be developed into any type of cell needed for treatment purposes.

On a hunch, Papadopoulos added human collagen to his soup of nutrients, genes and other ingredients needed to transform stem cells into Leydig cells. Collagen is a common growth matrix ingredient; previously, Papadopoulos used bovine or rat collagen, which are cheaper and mostly interchangeable with other forms of collagen, at least in early-stage experiments.

This time, the lab-grown Leydig cells produced testosterone – and the cells even looked the same as their naturally occurring counterparts under the microscope.

“It was none of the things we thought. We had tried different genes, chemicals, everything — nothing!” he said. “The human collagen was the secret sauce.”

 

[madman]

What’s next for low testosterone treatment

Next, Papadopoulos wants to test how well lab-grown Leydig cells function, and for how long, when they are transplanted into animal models of hypogonadism. He’s also eager to compare Leydig cells cultivated from skin cells from men with and without hypogonadism, to better understand the condition.
Human transplantation of Leydig cells is at least “a few years away,” he said.

 

[madman]

Reduced serum testosterone (T), or hypogonadism, affects millions of men and is associated with many pathologies, including infertility, cardiovascular diseases, metabolic syndrome, and decreased libido and sexual function. Administering T-replacement therapy (TRT) reverses many of the symptoms associated with low T levels. However, TRT is linked to side effects such as infertility and increased risk of prostate cancer and cardiovascular diseases. Thus, there is a need to obtain T-producing cells that could be used to treat hypogonadism via transplantation and reestablishment of T producing cell lineages in the body. T is synthesized by Leydig cells (LCs), proposed to derive from mesenchymal cells of mesonephric origin. Although mesenchymal cells have been successfully induced into LCs, the limited source and possible trauma to donors hinders their application to clinical therapies. Alternatively, human induced pluripotent stem cells (hiPSCs), which are expandable in culture and have the potential to differentiate into all somatic cell types, have become the emerging source of autologous cell therapies. We have successfully induced the differentiation of hiPSCs into either human Leydig-like (hLLCs) or adrenal-like cells (hALCs) using chemically defined culture conditions. Factors critical for the development of LCs were added to both culture systems. hLLCs expressed all steroidogenic genes and proteins important for T biosynthesis, synthesized T rather than cortisol, secreted steroid hormones in response to dibutyryl-cAMP and 22(R)-hydroxycholesterol, and displayed ultrastructural features resembling LCs. By contrast, hALCs synthesized cortisol rather than T. The success in generating hiPSC derived hLLCs with broad human LC (hLC) features supports the potential for hiPSC-based hLC regeneration.




Significance
Our results suggest that both androgen- and cortisol-producing human Leydig and adrenal cells can be induced from human induced pluripotent stem cells. This bidirectional approach offers insights into the events specifying different steroidogenic cell populations sharing developmental origins. More importantly, our study provides a way to generate possible transplantation materials for clinical therapies. Human Leydig-like cells could also be useful for in vitro studies of testicular development and pathologies of testis-relevant diseases, and for the discovery of new drugs inducing androgen formation for hypogonadism treatment.



In sum, our study describes an experimental approach with the potential of providing transplantation material for clinical therapy. Moreover, hiPSC-derived LCs can potentially be used for in vitro studies of testicular development and pathologies of testis relevant diseases and the discovery of new drugs that induce androgen formation and thus could treat hypogonadism (59).

 

[Systemlord]

However, treatment for low testosterone is linked to side effects such as infertility, increased risk of prostate cancer and cardiovascular diseases.

Sure oral testosterone is linked to cardiovascular risk, that is easily avoided with injectable T and tropicals.

While I'm glad researchers are working on better ways to get more testosterone out of us men, it seems the mainstream is clinging to old myths.

 

[madman]

Sure oral testosterone is linked to cardiovascular risk, that is easily avoided with injectable T and tropicals.

While I'm glad researchers are working on better ways to get more testosterone out of us men, it seems the mainstream is clinging to old myths.

Unfortunately!

It is the c-17 alpha alkylated AAS such as methyltestosterone (one of the first prescribed medications for low-t no longer in use), oxandrolone, stanozolol, methandrostenolone, oxymetholone, fluoxymesterone which have been shown to have negative effects on the liver as well as lipids as these orals are notorious for elevating liver enzymes, causing liver stress/inflammation, among more serious liver issues and are notorious for lowering HDL/increasing LDL.

Mind you oxandrolone has been shown to be safe when used long-term in low doses.

Also keep in mind that type of steroid used (c-17 alpha alkylated oral), dosage and duration of use will all have an impact on whether one experiences such effects let alone to what degree (severity).

Although they can be very harsh when abused many have been prescribed over the years especially in the past for certain medical disorders.....although many are no longer used for such purposes due to newly developed drugs which can achieve the same beneficial effect treating these medical disorders without the same risk.

I will say c-17 alpha alkylated orals are NOTORIOUSLY effective at lowering SHBG.....mind you I would not use for such purpose!

 

[Nelson Vergel]

Scientists use stem cells to restore testosterone