The study by Gutiérrez-Fernández and colleagues  shows that, in comparison with the controls, the administration of MSCs significantly improved the neural function, reduced apoptotic cell death, increased cell proliferation, and reduced reactive gliogenesis that causes scar formation.
Several mechanisms are proposed to explain the successful improvement of neural functional recovery through MSC administration: (a) exogenous tissue repair through migration/integration, (b) neuroprotection through the reduction of cell death or immunomodulation, (c) enhancement of endogenous tissue repair, and (d) plasticity promotion in synapse formation [1, 3, 5]. Brain tissue consists of a major functional unit (that is, the neurovascular unit) that contains neural and vascular cells. Thus, to achieve a more effective tissue reconstruction, both cell lineages need to be considered. Previous studies have shown that MSCs differentiate into neurons, glial cells, and vascular endothelial cells, in both in vitro and in vivo conditions [4, 5, 7–10]. However, in the related article and several other reports, there was no graft after the transvenous MSC administration, even though the immunological feature of MSCs can prevent allograft rejection [1, 8]. Therefore, the proposed cure mechanisms would be associated with the trophic factors secreted from MSCs. Correspondingly, the authors observe elevated levels of neurogenesis, synaprogenesis, oligodendrogenesis, and angiogenesis markers with increased levels of soluble factors in peri-infarct tissue 14 days after treatment with MSCs . Interestingly, the findings indicate that both MSCs administered just 30 minutes after ischemia can maintain the therapeutic effects on the brain repair process even 14 days later. In all comparative parameters, the present study shows no significant difference between the group that received BM-MSCs and the one that received AD-MSCs , whereas some reports indicate that each set of MSCs has different abilities in terms of secreting trophic factors [8, 10]. It is difficult to define the perfect integrity of each set of MSCs. In the most popular protocol, MSCs are currently isolated with a few cell surface markers [4, 5]. The different results are expected to be verified by further findings about cell quality and integrity.
Nevertheless, the multipotency of MSCs would surely be beneficial if the MSCs were to integrate into the target. The previous study by Gutiérrez-Fernández and colleagues  and other reports indicate that transarterial administration would deliver MSCs to the peri-infarct area , implying the possibility of application to neuroendovascular therapies through a catheter. The neural induction potential of MSCs has been extensively examined . Still, further analyses are expected to be conducted on gene regulation mechanisms, including epigenetics while neural differentiation is occurring. In this context, an analysis of RNA and microRNA profiles was recently reported . Also, in vitro comparative studies on the molecular biological characteristics have begun to be published, and differences among the various MSCs (BM-MSCs, AD-MSCs, and so on) have been detected [10, 12]. The development of in vitro analysis will contribute to customizing the selection of appropriate graft MSCs in accordance with individual conditions.