Sertoli cells for cell transplantation: pre‐clinical studies and future perspectives

Abstract

Sertoli cells are located in the testes where they control several key functions in spermatogenesis. Over the past 30 years, Sertoli cells have been upgraded from a simple scaffold-like structural system to a dynamic functional system of intercellular support that delivers potent immunomodulatory and trophic factors. Since the discovery of new Sertoli cell secretory products, these cells have been utilized in experimental cell transplantation and co-transplantation protocols aimed at treating both chronic inflammatory and degenerative disorders. For these reasons, this work reviews the application of both naked and microencapsulated Sertoli cells used in cell transplantation studies of several chronic or autoimmune diseases such as diabetes mellitus, Laron dwarfism, and Duchenne muscular dystrophy and in studies aimed at the prevention of skin allograft rejection.

Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation

“…They also have the ability to modulate the immune response through the production of immune regulatory factors. This means that Sertoli cells may also be useful in a variety of clinical applications, such as the use of encapsulated Sertoli cells to deliver immune modulatory and trophic factors [47][48][49][50], as a cell-based drug delivery system [51], or being engineered to express therapeutic proteins [52][53][54], which may be used to treat cancer, chronic, and autoimmune diseases. Therefore, understanding the factors involved in human Sertoli cell maturation may also have relevance to these developing fields of clinical research.…”

Mapping molecular pathways for embryonic Sertoli cells derivation based on differentiation model of mouse embryonic stem cells

“…Then, the manipulation of the factors could be regulated based on these results. (2) In embryonic development, Sf1 expressed during 9.75-12.5 dpc. Wt1, Gata4, Sox9, and Dmrt1 kept expression since they were activated.…”

“…In mammalian embryo, Sertoli cells play a key role in the onset of male determination and gonadal development [1]. The mechanism of derivation and development of Sertoli cells has a close relevance with some reproductive disorders [2][3][4][5]. However, the molecular pathways in the derivation of Sertoli cells in embryos are still unclear.…”

Induction of Sertoli cells from human fibroblasts by NR5A1 and GATA4

“…Another prominent role of Sertoli cells is the creation of an immune-privileged environment to protect germ cells from immune attacks of lymphocytes. Many studies have documented that Sertoli cells secrete factors that suppress the proliferation of T cells, B cells and NK cells 14,45 , including the suppression of IL-2 from T cells 52 . Our results indicate that culture media incubated with hiSCs suppress the proliferation of Jurkat cells (the immortalized cell line of human T lymphocytes) and reduce IL-2 production in Jurkat cells treated with hiSC-conditioned media (Fig.…”

“…The immune-privileged potential of Sertoli cells has been utilized in many allo- and xeno-grafts to reduce the immune response in the field of cell transplantation 11–13 . Preclinical studies have transplanted Sertoli cells with various other cell types for the treatment of diabetes, neurodegenerative diseases, Duchenne muscular dystrophy, skin allografts and other diseases 14 .…”