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Characterization of Human Mesenchymal Stem Cells Isolated from the Testis 时间:2018-09-06 20:25   来源:未知   作者:admin   点击: 次 Abstract:Mesenchymal stem cells hold great promise for regenerative medicine as they can be easily isolated from different sources such as adipose tissue, bone marrow, and umbilical cord blood. Spontaneously arising pluripotent stem cells can be obtained in culture from murine spermatogonial stem cells (SSCs), while the pluripotency of the human counterpart remains a matter of debate. Recent gene expression profiling studies have demonstrated that embryonic stem cell- (ESC-) like cells obtained from the human testis are indeed closer to mesenchymal stem cells (MSCs) than to pluripotent stem cells. Here, we confirm that colonies derived from human testicular cultures, with our isolation protocol, are of mesenchymal origin and do not arise from spermatogonial stem cells (SSCs). The testis, thus, provides an important and accessible source of MSCs (tMSCs) that can be potentially used for nephrotoxicity testing in vitro. We further demonstrate, for the first time, that tMSCs are able to secrete microvesicles that could possibly be applied to the treatment of various chronic diseases, such as those affecting the kidney.
1. Introduction
  Mesenchymal stem cells (MSCs) are multipotent stem cells first postulated by Owen et al. to be derived from bone marrow [1]. Since then, this stromal cell type has been found in a myriad of different tissues [2–4]. As MSCs are able to home to sites of inflammation and differentiate into various cell types and are immunomodulatory, they are ideal candidates for clinical applications. Unlike multipotent stem cells, SSCs are unipotent stem cells that reside on the basal membrane of the testis and can give rise only to spermatozoa. SSCs are defined by their ability to balance between self-renewal and differentiation, a feature which is supported by Sertoli and stromal cells that represent the main components of the SSC niche [5]. The study of SSCs has always been challenging as they are very limited in number [6, 7], and specific markers have not yet been identified [8].
  Intriguingly, murine SSCs, under specific culture conditions, are able to spontaneously convert into pluripotent embryonic-like stem cells, known as germline cell-derived pluripotent stem cells (GPSCs) [9–12]. Recently, a number of groups have claimed that pluripotent stem cells can be derived from unipotent human SSCs [13, 14]. Nevertheless, these findings have been subsequently challenged [15], demonstrating that these “embryonic-like colonies” have an expression profile more similar to that of fibroblasts than to that of embryonic stem cells (ESCs) [16] and are, in fact, of mesenchymal origin [17, 18].
Here, we confirm that a mesenchymal population can be easily established from small human biopsies without employing any particular separation protocol. Interestingly, we demonstrate that these testicular MSCs (tMSCs) can be established from very small testis biopsies making them an attractive and novel source of MSC for cell therapy. Furthermore, we evaluate the microvesicle profile of these tMSCs derived from the human testis, which was never shown before. The therapeutic potential of extracellular vesicles is very broad, with applications including as a drug delivery route and as biomarkers for diagnosis [19, 20]. Extracellular vesicles extracted from stem cells may be used for treatment of many diseases including those affecting the kidney [21–23].