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.

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Figure 1: The rise of MSC therapy.
Figure 2: Immune suppression enables immune evasion.
Figure 3: Strategies to facilitate MSC immune evasion.

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Acknowledgements

This work was supported by National Institutes of Health grant HL095722, Department of Defense grant no. W81XWH-13-1-0305 and by a Movember–Prostate Cancer Foundation Challenge Award to J.M.K. J.A.A. was supported by the Hugh Hampton Young Memorial Fellowship.

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Correspondence to Jeffrey M Karp.

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J.M.K. is a paid consultant of Sanofi and Stempeutics in the area of regenerative medicine and mesenchymal stem cells.

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Ankrum, J., Ong, J. & Karp, J. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol 32, 252–260 (2014). https://doi.org/10.1038/nbt.2816

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