Abstract:Immune-privileged Sertoli cells (SCs) exhibit long-term survival after allotransplantation or xenotransplantation, suggesting they can be used as a vehicle for cell-based gene therapy. Previously, we demonstrated that SCs engineered to secrete insulin by using an adenoviral vector normalized blood glucose levels in diabetic mice. However, the expression of insulin was transient, and the use of immunocompromised mice did not address the question of whether SCs can stably express insulin in immunocompetent anima… Show more
“….). These unique immunomodulatory properties suggest that Sertoli cells are not only important for the overall protection and development of germ cells, they have therapeutic potential beyond the testis where they can protect co‐grafted cells and even be engineered to express clinically relevant proteins like insulin to treat diabetes or neurotrophin‐3 to treat spinal cord injury (Pelletier, ; Halley et al ., ; Kaur et al ., 2014b, 2015). Sertoli cells create this immune privileged environment by expressing immunoregulatory factors that actively suppress innate, humoral and cell‐mediated immune responses while at the same time inducing regulatory immune cells (regulatory T cells and M2 macrophages).…”
Section: Sertoli Cells and Testis Immune Privilegementioning
SUMMARY
It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular ‘nurse cell’, not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell’s role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways.
“….). These unique immunomodulatory properties suggest that Sertoli cells are not only important for the overall protection and development of germ cells, they have therapeutic potential beyond the testis where they can protect co‐grafted cells and even be engineered to express clinically relevant proteins like insulin to treat diabetes or neurotrophin‐3 to treat spinal cord injury (Pelletier, ; Halley et al ., ; Kaur et al ., 2014b, 2015). Sertoli cells create this immune privileged environment by expressing immunoregulatory factors that actively suppress innate, humoral and cell‐mediated immune responses while at the same time inducing regulatory immune cells (regulatory T cells and M2 macrophages).…”
Section: Sertoli Cells and Testis Immune Privilegementioning
SUMMARY
It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular ‘nurse cell’, not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell’s role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways.
“…Firstly, Sertoli cells could secrete insulin persistently after being genetically transformed [7], which may provide new therapeutic approach for diabetes. Secondly, Sertoli cells could be reprogrammed to the pluripotent stem cells and to morphologic, phenotypic and functional neural stem cells by transferring certain genes or transcription factors [8–10].…”
Sertoli cells are required for normal spermatogenesis and they can be reprogrammed to other types of functional cells. However, the number of primary Sertoli cells is rare and human Sertoli cell line is unavailable. In this study, we have for the first time reported a stable human Sertoli cell line, namely hS1 cells, by overexpression of human telomerase. The hS1 cells expressed a number of hallmarks for human Sertoli cells, including SOX9, WT1, GDNF, SCF, BMP4, BMP6, GATA4, and VIM, and they were negative for 3β-HSD, SMA, and VASA. Higher levels of AR and FSHR were observed in hS1 cells compared to primary human Sertoli cells. Microarray analysis showed that 70.4% of global gene profiles of hS1 cells were similar to primary human Sertoli cells. Proliferation assay demonstrated that hS1 cells proliferated rapidly and they could be passaged for more than 30 times in 6 months. Neither Y chromosome microdeletion nor tumorgenesis was detected in this cell line and 90% normal karyotypes existed in hS1 cells. Collectively, we have established the first human Sertoli cell line with phenotype of primary human Sertoli cells, an unlimited proliferation potential and high safety, which could offer sufficient human Sertoli cells for basic research as well as reproductive and regenerative medicine.
“…Thirdly, Sertoli cells have been reprogrammed to generating the induced pluripotent stem (iPS) cells [ 43 ], and notably, Sertoli cells can be directly converted into morphologic, phenotypic, and functional neural stem cells [ 44 ]. Sertoli cells have been engineered to secrete the necessary proteins capable of restoring normal cell and metabolic function [ 45 ], indicating extreme promise of Sertoli cells to be exploited in cell-based therapy. Thus, Sertoli cells may have important implications for disease modeling and regenerative medicine.…”
BackgroundSertoli cells play key roles in regulating spermatogenesis and testis development by providing structural and nutritional supports. Recent studies demonstrate that Sertoli cells can be converted into functional neural stem cells. Adult Sertoli cells have previously been considered the terminally differentiated cells with a fixed and unmodifiable population after puberty. However, this concept has been challenged. Since the number of adult human Sertoli cells is limited, it is essential to culture these cells for a long period and expand them to obtain sufficient cells for their basic research and clinic applications. Nevertheless, the studies on human Sertoli cells are restricted, because it is difficult to get access to human testis tissues.ResultsHere we isolated adult human Sertoli cells with a high purity and viability from obstructive azoospermia patients with normal spermatogenesis. Adult human Sertoli cells were cultured with DMEM/F12 and fetal bovine serum for 2 months, and they could be expanded with a 59,049-fold increase of cell numbers. Morphology, phenotypic characteristics, and the signaling pathways of adult human Sertoli cells from different passages were compared. Significantly, adult human Sertoli cells assumed similar morphological features, stable global gene expression profiles and numerous proteins, and activation of AKT and SMAD1/5 during long-period culture.ConclusionsThis study demonstrates that adult human Sertoli cells can be cultured for a long period and expanded with remarkable increase of cell numbers whilst maintaining their primary morphology, phenotype and signaling pathways. This study could provide adequate human Sertoli cells for reproductive and regenerative medicine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12964-015-0101-2) contains supplementary material, which is available to authorized users.
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