Mesenchymal stem cells: immune evasive, not immune privileged

Abstract

The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) may be exploited for treatment of a multitude of inflammatory conditions. MSCs have long been reported to be hypoimmunogenic or ‘immune privileged’; this property is thought to enable MSC transplantation across major histocompatibility barriers and the creation of off-the-shelf therapies consisting of MSCs grown in culture. However, recent studies describing generation of antibodies against and immune rejection of allogeneic donor MSCs suggest that MSCs may not actually be immune privileged. Nevertheless, whether rejection of donor MSCs influences the efficacy of allogeneic MSC therapies is not known, and no definitive clinical advantage of autologous MSCs over allogeneic MSCs has been demonstrated to date. Although MSCs may exert therapeutic function through a brief ‘hit and run’ mechanism, protecting MSCs from immune detection and prolonging their persistence in vivo may improve clinical outcomes and prevent patient sensitization toward donor antigens.

Mesenchymal stem cell-based therapy for ischemic stroke

“…MSCs can exert profound immunosuppression both in vitro and in vivo by inhibiting the proliferation of T-cells, natural killer cells, and dendritic cells [32]. MSC have also been reported to induce proliferation of immune suppressive Treg cells, at least in part by inducing the differentiation of monocytes towards resident M2 macrophages [33].…”

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

“…The characteristics allow MSC therapy from third party donors for acute GVHD. However, the production of allo-reactive antibodies to MSCs and the rejection of transplanted MSCs have described [26]. Long term persistence of MSCs was not observed after HSCT and high-dose MSCs transplantation for children with severe osteogenesis imperfecta [27].…”

Médecine régénératrice du disque intervertébral

“…Des cellules souches non différenciées, répondant aux signaux locaux une fois injectées dans le DIV, pourraient se différencier en un type cellulaire compatible avec une régénérescence discale. Cette hypothèse se fonde sur les propriétés de plasticité des CSM [14], ainsi que sur leurs propriétés anti-inflammatoires et trophiques 1 [15,16]. Pour le moment, à notre connaissance, cette plasticité en réponse à l'environnement n'a pas été démontrée pour les cellules implantées dans un site discal.…”

“…En effet, il a été démontré que les CSM présentent des propriétés immunogéniques faibles [16,25]. De plus, l'environnement discal constitue un site immunoprivilégié qui pourrait limiter ce risque [26].…”