Sertoli Cells Enhance Formation of Capillary-Like Structures in Vitro

Abstract

Sertoli cells isolated from the testis (referred to as extratesticular Sertoli cells) have been shown to facilitate allo-and xenogeneic cell transplantations. It appears likely that the ability of these cells to enhance the success of cell engraftment is due, in part, to the retention of their intratesticular functions of trophic support and immunoprotection. Sertoli cells also are involved in the regulation of angiogenesis in the testis, which may also contribute to enhanced cell engraftment success facilitated by extratesticular Sertoli cells. Because the maintenance of the cell's intratesticular angiogenic function has not yet been evaluated for extratesticular Sertoli cells, this study examined the cell's ability to enhance angiogenesis in vitro. Sertoli cell conditioned media were derived from isolated rat Sertoli cell cultures and used in a rat aortic model of induced angiogenesis, in endothelial and smooth muscle cell monocultures, and in endothelial smooth muscle cocultures. An angiogenic rat cytokine array identified angiogenic factors in the control and conditioned media. Aorta sections incubated with Sertoli cell conditioned media showed a marked increase in the formation of capillary-like structures when compared to controls. Likewise, endothelial cells incubated in conditioned media organized into capillary-like structures not observed when incubated in control media. In coculture, smooth muscle cells were associated with endothelial cell-derived capillary-like structures only when incubated in conditioned media. Cytokine arrays indicated the presence and a qualitative increase of specific angiogenic growth factors in Sertoli cell conditioned media not observed in control media. Results indicate that extratesticular Sertoli cells retain their intratesticular angiogenic function in vitro.

Expression of cell adhesion molecules, chemokines and chemokine receptors involved in leukocyte traffic in rats undergoing autoimmune orchitis

“…In seasonal breeders, increased angiogenesis and rapid renewal of microvasculature is fundamental for physiologic testicular recrudescence (Mayerhofer et al 1989). Sertoli cells (which remain attached to the ST walls even in rats with severe EAO) and Leydig cells have been shown to have an angiogenic function (Collin & Bergh 1996, Golat & Cameron 2008. Leukocyte infiltration into the testicular interstitium is a key process in the pathogenesis of testicular inflammation.…”

Loss of Smad4 in Sertoli and Leydig Cells Leads to Testicular Dysgenesis and Hemorrhagic Tumor Formation in Mice1

“…Loss of Smad4 also promotes angiogenesis in a number of cancers, leading to the hypothesis that SMAD4 functions as an angiogenic switch within tumors [39]. Like many epithelial lineages, Sertoli cells produce a number of angiogenic growth factors and Sertoli cell-conditioned media is even known to enhance the formation of capillary-like structures in vitro [40]. reported in a mouse model in which SMADs 1 and 5 were simultaneously knocked out using Amhr2-Cre; specifically, Smad1-Smad5 dKO mice developed metastatic sex cord stromal tumors with Sertoli and Leydig cell differentiation and hemorrhagic ascites [43].…”

The Battle of the Sexes for Stroke Therapy: Female- Versus Male-Derived Stem Cells

“…Menstrual blood stem cells may also promote anti-inflammatory cytokines, since their addition to mixed lymphocyte cultures resulted in stimulation of IL-4 and inhibition of TNF after endotoxin stimulation [26] and the monthly shedding of the endometrium during menstruation supports a role in angiogenesis and tissue replacement. Sertoli cells have also been shown to secrete proangiogenic factors [52] as well as promote tolerance when cotransplanted [53]. These studies suggest that menstrual blood stem cells and Sertoli cells could both be beneficial via modulatory means.…”

“…The gap junctions of the tubules, specifically those between the Sertoli cells and germ cells, aid in communication of the morphology of the sperm cells. Sertoli cells have been shown to augment engraftment of both allogenic and xenogenic cells and aid in the therapy for disorders such as Parkinson’s Disease, type 1 diabetes, and Huntington’s Disease [52,70-73]. …”

“…They also express regulatory proteins and nutritive factors as well which assist in the development of the testis and stimulate the growth of germ cells [28,74-79]. Contributing to germ cell viability is essential in protecting against immune detection and possible rejection [52]. Their ability to provide immunogenic protection means that the testes are considered an immunologic “privileged” organ site [28].…”