Do porcine Sertoli cells represent an opportunity for Duchenne muscular dystrophy?

Sara Chiappalupi,Rosario Donato,Francesca Riuzzi,Laura Salvadori,Riccardo Calafiore,Giovanni Luca,Guglielmo Sorci

doi:10.1111/cpr.12599

Abstract

Sertoli cells (SeC) are responsible for the immunoprivileged status of the testis thanks to which allogeneic or xenogeneic engraftments can survive without pharmacological immune suppression if co‐injected with SeC. This peculiar ability of SeC is dependent on secretion of a plethora of factors including maturation factors, hormones, growth factors, cytokines and immunomodulatory factors. The anti‐inflammatory and trophic properties of SeC have been largely exploited in several experimental models of diseases, diabetes being the most studied. Duchenne muscular dystrophy (DMD) is a lethal X‐linked recessive pathology in which lack of functional dystrophin leads to progressive muscle degeneration culminating in loss of locomotion and premature death. Despite a huge effort to find a cure, DMD patients are currently treated with anti‐inflammatory steroids. Recently, encapsulated porcine SeC (MC‐SeC) have been injected ip in the absence of immunosuppression in an animal model of DMD resulting in reduction of muscle inflammation and amelioration of muscle morphology and functionality, thus opening an additional avenue in the treatment of DMD. The novel protocol is endowed with the advantage of being potentially applicable to all the cohort of DMD patients regardless of the mutation. This mini‐review addresses several issues linked to the possible use of MC‐SeC injected ip in dystrophic people.

Highlights

Sertoli cells (SeC) are major component of the seminiferous tubules of the testis where they contribute to the development of germ cells and protect germ cells from the attack by the host immune system.[1,2] newly synthesized markers on germ cell surface would be recognized as non‐self by the immune system, as this latter becomes mature before spermatogenesis starts
SeC exert their double role (a) by creating a physical barrier made of adjacent SeC linked together with tight junctions, isolating the lumen of seminiferous tubules from the interstitial fluid, and (b) by secreting a plethora of trophic and immunomodulatory factors.[3,4]. This latter ability of SeC has prompted researchers to use them in many experimental models of diseases in which supplying trophic factors, abating inflammation or modulating the immune system ac‐ tivity might result in reversion or attenuation of the pathology.[2,5]
The pro‐ gressive muscle degeneration subsequent to lack of dystrophin creates a condition of chronic inflammation that culminates in the progressive substitution of myofibres with fibrous and adipose tis‐ sues, impaired locomotion and premature death

Summary

| INTRODUCTION

Sertoli cells (SeC) are major component of the seminiferous tubules of the testis where they contribute to the development of germ cells and protect germ cells from the attack by the host immune system.[1,2] newly synthesized markers on germ cell surface would be recognized as non‐self by the immune system, as this latter becomes mature before spermatogenesis starts. SeC exert their double role (a) by creating a physical barrier (the blood‐testis barrier, BTB) made of adjacent SeC linked together with tight junctions, isolating the lumen of seminiferous tubules from the interstitial fluid, and (b) by secreting a plethora of trophic and immunomodulatory factors.[3,4] This latter ability of SeC has prompted researchers to use them in many experimental models of diseases in which supplying trophic factors, abating inflammation or modulating the immune system ac‐ tivity might result in reversion or attenuation of the pathology.[2,5]. Cell therapy represents a second front of therapeutic ap‐ proaches to DMD It tries to use different cell types (especially, satel‐ lite cells/myoblasts, mesoangioblasts and induced pluripotent stem cells [iPSC]) from healthy donors or genetically engineered cells from the patients themselves to obtain the re‐expression of dystrophin in muscle tissue and recovery of muscle performance.[51-54]. Mesoangioblasts (ie, cells associated with the walls of large vessels) represent one of the most promising

Limitations

Findings

| CONCLUSIONS