Turning Stem Cells in Testes into Testosterone-Producing Cells in a Sustainable Culture System


A research effort led by scientists at Johns Hopkins Bloomberg School of Public Health, in collaboration with researchers from Wenzhou Medical university of China has successfully made testosterone-producing stem cells in culture that can be propagated in the laboratory.

Haolin Chen of the Bloomberg School of Public Health noted that testosterone treatments often produce spikes and troughs in testosterone concentrations that can cause a variety of side effects. Administering testosterone-producing cells might very well prevent these wide variations in testosterone production and decrease the potential side effects. Low testosterone in males has been linked to increased mortality, in addition to depression, decreased cognition and immune function, increase body and reduced muscle mass, and poor healing.

A group of cells called Leydig cells in between the seminiferous tubules in the testes of males typically produce testosterone in response to stimulation by a hormone called luteinizing hormone (LH), which is made by the anterior pituitary. Leydig cells produce testosterone in a rather stable, constant fashion, in contradistinction to the injections that are given to males with low testosterone levels.

Unfortunately, keeping testosterone-producing Leydig cells or Leydig cell progenitors alive in culture has proven rather difficult. To address this problem, Chen and his collaborators started adding combinations of growth factors to the cells to determine if any cocktails of growth factors or nutrients could keep the cells alive. Fortunately, they came upon a combination of platelet-derived growth factor, basic fibroblast growth factor, activin, and a molecule called desert hedgehog that stimulated the proliferation of the Leydig cell precursors. Desert hedgehog and activin in general drove the differentiation of these cells into testosterone-producing Leydig cells.

Further work revealed a cell surface protein called CD90 that earmarked all the stem cells in the testes of rats that could be differentiated into Leydig cells.

Chen thinks that the primary culture-differentiation system that he and his colleagues have devised could serve as a useful model system for stem cells in general, or as a clinically relevant system that could produce testosterone-producing stem cells for males with low testosterone levels.

“Our work could eventually offer a whole new therapy for individuals with low testosterone,” said Chen.

This work was published in the Proceedings of the National Academy of Sciences USA, 2016; 113(10): 2666 DOI:10.1073/pnas.1519395113.

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mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).