The Neuroendocrine Leydig Cells and their Stem Cell Progenitors, the Pericytes (Advances in Anatomy, Embryology and Cell Biology)

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9783642005121: The Neuroendocrine Leydig Cells and their Stem Cell Progenitors, the Pericytes (Advances in Anatomy, Embryology and Cell Biology)
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cells, and the testicular localization of the intermediate filament protein nestin, known to be expressed in neural stem cells, by our group was the first step to define mural cells (pericytes and vascular smooth muscle cells) of the testis microvascu- ture as the stem/progenitor cells of the adult Leydig cells. In summary, we were able to demonstrate specific proliferation of vascular progenitors and their subsequent transdifferentiation into steroidogenic Leydig cells, which – in addition – rapidly acquire neuronal and glial properties. Since both newly developed fetal and adult Leydig cell populations show the same features, a common origin of both popu- tions seems likely. Pericytes are distributed throughout the body, and there is convincing evidence for their stem/progenitor cell properties in diverse organs. Under appropriate (locally defined) conditions these pericytes, which reside in the vascular stem cell niche as dormant stem cells, become activated, proliferate, migrate and differentiate towards different somatic cell types of the body. Since most mesenchymal stem/ progenitor cell types exhibit essential similarity to pericytes and certain mesenchymal stem cells represent pericyte descendants, we propose that mesenchymal stem cells in the perivascular niche are daughter cells of pericytes. Thus, pericytes are promising candidates for ancestor cells of all adult stem cells in the organism. There is strong evidence that early stem cells (cells arising during embryogenesis), such as the pericytes, exhibit both mesodermal and neural progeny, which might explain the neuroendocrine properties of the Leydig cells.

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The Leydig cells of the testis represent the main source of androgens. The idea of Leydig cells as endocrine cells has been the leading characteristic of this interesting cell population till now. Our studies of the last 2 decades allowed us to reveal a new important feature of Leydig cells that is their obvious similarity with structures of the central and peripheral nervous system. This includes the expression of neurohormones, neurotransmitters, neuropeptides and glial cell antigens. In this way, it became evident that in addition to the well established control by steroids and systemic hormones, important local auto- and paracrine control mechanisms of testicular functions exist.

Thus, the Leydig cells represent a specialized cell population with both endocrine and neuroendocrine properties. The discovery of the neuroendocrine features of Leydig cells gave rise to the hypothesis of a potential neuroectodermal and/or neural crest origin of testicular Leydig cells. In an experimental animal model we revealed that adult Leydig cells originate by transdifferentiation from stem/progenitor cells (pericytes and smooth muscle cells), underlying the close relationship of Leydig cells with testis microvasculature. This and the supporting data from the literature provided the basis for revealing the pericytes as a common adult stem cell type of mammalian species. Distributed by the microvasculature through the entire body, the pericyte, acting as a resting early pluripotent adult stem cell, provides an ingenious system to assure the maintenance, physiological repair and regeneration of organs, each under the influence of specific local environmental factors.

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