Effect of the transplantation type on the neuroprotective properties of mesenchymal stromal cells

Abstract

Many preclinical studies using adult Mesenchymal Stromal Cells (MSCs) for neurodegenerative diseases show promising results. However, there is a lack of concordance between the extensive research on MSC neuroprotection and clinical translation as evidenced by the few clinical trials currently using this strategy. A major discordance between animal models and patients is the type of transplant. Commonly, human cells are tested in animal models but this is a xenotransplant. As a rule, though, patients are either treated with autologous (syngeneic) or allogeneic cells. However, the crosstalk between the grafted cells and the host tissue is something that, despite its importance, is not being systematically investigated. We will show here that the therapeutic outcome, host homeostasis and immune response to intravitreal administered bone‐marrow MSCs radically changes depending on the type of transplantation. As expected, xenografts are the more damaging, followed by allografts with or without immunosuppression. Syngrafts are not completely innocuous, but they do not alter neuronal functionality, making them the safest and the best ones to neuroprotect and to induce axonal regeneration. In conclusion, the transplantation modality should be taken into consideration when conducting preclinical studies if we intend a more realistic translation into clinical practice.