Mesenchymal stem cells induce immunomodulation of microglia to repair brain damage after stroke - a critical analysis of the literature

Abstract

Globally, stroke is a main cause of morbidity and mortality. Its consequences not only affect health, but also resources and sustainability with the continuous rise of worldwide stroke burden. Stroke survivors have limited therapeutic options and often remain with significant disabilities. Current medical interventions to provide safe and effective neurological recovery are inadequate. This sheds the light on the urgent necessity for novel treatments. In animal models of stroke, transplantation of mesenchymal stem cells (MSCs) and neural stem cells (NSCs) has been shown as a promising regenerative therapy for stroke. However, the mechanism(s) are not fully understood. Observed beneficial effects of stem cells include immunomodulatory actions on microglia, shifting their inflammatory response into an anti-inflammatory phenotype favouring both regeneration and neuroprotection. The present critical appraisal tests the hypothesis that MSCs are more effective than NSCs at inducing immunomodulation of microglia to repair brain damage after stroke. The results of this critical analysis indicate that the MSC experiments provided more robust evidence of early and long-lasting positive immunomodulatory effects than the NSC experiments. However, developing more specific microglial markers, distinct from infiltrated macrophages, is required. In addition, transplanting stem cells into a bigger animal model is recommended, more akin to human stroke. Methodological best practice in study design such as the inclusion of randomisation and blinding should be adopted to reduce bias and maximise reliability. In conclusion, this thesis proves that MSCs can be more effective than NSCs at inducing immunomodulation of microglia to repair brain damage after stroke.