Mesenchymal Stromal Cells in Ischemic Brain Injury

Abstract

Ischemic brain injury represents a major cause of death worldwide with limited treatment options with a narrow therapeutic window. Accordingly, novel treatments that extend the treatment from the early neuroprotective stage to the late regenerative phase may accommodate a much larger number of stroke patients. To this end, stem cell-based regenerative therapies may address this unmet clinical need. Several stem cell therapies have been tested as potentially exhibiting the capacity to regenerate the stroke brain. Based on the long track record and safety profile of transplantable stem cells for hematologic diseases, bone marrow-derived mesenchymal stromal cells or mesenchymal stromal cells have been widely tested in stroke animal models and have reached clinical trials. However, despite the translational promise of MSCs, probing cell function remains to be fully elucidated. Recognizing the multi-pronged cell death and survival processes that accompany stroke, here we review the literature on MSC definition, characterization, and mechanism of action in an effort to gain a better understanding towards optimizing its applications and functional outcomes in stroke.

Keywords: brain injury; mesenchymal stem cells; mesenchymal stromal cells; stem cells; stroke.

Figure 1

MSC grafts in the ischemic stroke brain. MSCs may migrate and repopulate the stroke brain, differentiate to neural cells and release trophic and anti-inflammatory factors and extracellular vesicles, altogether creating a secretome profile of a regenerative brain. While these may not fully repair the lost tissue, MSCs may be able to regenerate the spared tissue (i.e., penumbra and peri-infarct area) surrounding the necrotic infarct core and the adjacent penumbra or peri-infarct area.

Figure 2

MSC standardization and optimization leading to improved functional outcomes. The standardization of the treatment and classification of MSCs combined with the standardization of MSC administration can increase their clinical applications in clinical trials and settings, which may lead to improved functional outcomes.