In a new study, researchers from Sun Yat-sen University identified the characteristics of testicular Leydig stem cells (SLCs) as potential cell sources for the treatment of testosterone deficiency in men. The research was published in the November 21 issue of Cell Research.
The author of the paper is Professor Andy Peng Xiang of Zhongshan Medical College of Sun Yat-Sen University. He is mainly engaged in stem cell and developmental biology, gene knockout and transgenic animal research. He has published more than 30 research papers so far.
Testosterone is an important hormone in males and has a wide range of physiological effects. Testosterone plays an irreplaceable role in all physiological and pathological processes from embryo formation to aging, affecting not only gender differentiation, growth and development, but also various physiological functions of the body. It also affects men's mental mood and society. Psychological behavior (Extended reading: Science is amazingly discovered: hormones blow the nerve retreat, shaping the difference between men and women). Testosterone deficiency is a clinically common male pathophysiological state, which can occur in all ages of men and has adverse effects on multiple organ system functions of the body.
Leydig cells (LCs) are localized in the testicular stroma and are the main source of testosterone in men, essential for male secondary sexual formation and spermatogenesis. According to a recent epidemiological survey, more than 4.5 million men in the United States have symptoms associated with testosterone deficiency, such as changes in body composition, fatigue, sexual dysfunction, depression, and decreased cognitive function. Although LC transplantation has proven to be an ideal treatment for testosterone deficiency. However, the study found that mature LCs could not proliferate, the survival time was short, and the constructed tissues could not maintain function for a long time, thus limiting the efficacy of LC transplantation therapy.
Like other functionally differentiated cells, testicular LCs are also derived from the original undifferentiated Leydig stem cells. LCs in the testis maintain the dynamic stability of the population by the proliferation and differentiation of SLCs. Because SLCs have the ability of androgen secretion and self-renewal, and may be affected by the innate regulatory mechanism of the body after implantation, which is more in line with physiological requirements, it has become the most promising seed cell for the construction of androgen secretion. However, for a long time, SLCs have hindered their isolation and purification due to the lack of specific markers.
In this new article, the researchers report the use of flow cytometry combined with in vitro functional biology experiments to identify and isolate SLCs based on Nestin (Nes) expression. In a mouse model driven by the Nes promoter to drive GFP, they observed that some Nes-GFP+ cells were localized in the interstitial compartment normally present in SLCs and confirmed that these Nes-GFP+ cells express LIFR and PDGFR-α, not a LC lineage marker. The researchers further observed that under certain conditions, these cells can form clones and have the ability to self-renew and proliferate in vitro, and can differentiate into neural or mesenchymal cell lineages and LCs, and have the ability to produce testosterone.
When transplanted into the testes of LC-destroyed or aging models, the researchers found that these Nes-GFP+ cells were transplanted into the stroma, locally increasing testosterone production and subsequently accelerating meiosis and meiosis. Recovery of germ cells after division. In addition, they further confirmed that CD51 may be similar to Nestin and is a cell surface marker for SLCs.
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