Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible

Abstract

The testis as an immune-privileged site allows long-term survival of allogeneic and xenogeneic transplants. Testicular Sertoli cells (SCs) play a major role in this immunoprotection and have been used to create an ectopic immune-privileged environment that prolongs survival of co-transplanted allogeneic and xenogeneic cells, including pancreatic islets and neurons. Extended survival of such grafts testifies to the immunoprotective properties of SCs. However, there is still variability in the survival rates of the co-grafted cells and rarely are 100% of the grafts protected. This emphasizes the need to learn more about what is involved in creating the optimal immunoprotective milieu. Several parameters including organization of the SCs into tubule-like structures and the production of immunomodulatory factors by SCs, specifically complement inhibitors, cytokines, and cytotoxic lymphocyte inhibitors, are likely important. In addition, an intricate interplay between several of these factors may be responsible for providing the most ideal environment for protection of the co-transplants by SCs. In this review, we will also briefly describe a novel use for the immune-privileged abilities of SCs; engineering them to deliver therapeutic proteins for the treatment of diseases like diabetes and Parkinson's disease. In conclusion, further studies and more detailed analysis of the mechanisms involved in creating the immune-protective environment by SCs may make their application in co-transplantation and as engineered cells clinically feasible.

Testicular defense systems: immune privilege and innate immunity

“…11 In the 1970s to the 1980s, a variety of allografts and xenografts were found to function in the testis for an extended amount of time. 12 Notably, the survival time of insulin-secreting xenogeneic islets is significantly prolonged in the testis compared to other recipient sites. 13 The testicular properties that provide immune privilege can also protect auto-antigenic germ cells from detrimental immune responses.…”

Blood–testis barrier and Sertoli cell function: lessons from SCCx43KO mice

“…Finally, in recent publications it was elucidated that SC might help to establish extra-testicular long term immuno-privileged allogenic and xenogeneic transplants (Korbutt et al 1997, Mital et al 2010. The production of immunomodulatory factors by SC and the protective barrier capacity of SC could be used in transplants (e.g.…”

“…On the other hand, specific substances (e.g. insulin) could transverse through the SC and from there be distributed throughout the patient (Mital et al 2010). One advantage for implementing the CX43-deficient SC for allogenic and xenogeneic transplants would be the over-synthesis of tight junction proteins causing a possible tighter and more protective immunological barrier.…”

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

“…The testis is considered an immune-privileged site, and testicular Sertoli cells (SCs) have been identified as key players for conferring this immune privilege (Selawry 1994, Dufour et al 2003. SCs mechanically segregate germ cell autoantigens by means of the blood-tubular barrier and create an effective immune-privileged environment that protects germ cells from invading pathogens (Riccioli et al 2006, Mital et al 2010. Therefore, the protection of germ cells from infections in the seminiferous tubules is of primary importance, because bacterial infections can seriously damage reproductive functions.…”