The potential of a combined cell-based therapy and rehabilitation approach for stroke recovery

Activation of neuroprotective and particularly later neurorestorative mechanisms after stroke attempts to restore or compensate for lost functions. This potentially opens a wide window for restorative therapies to promote brain repair and improve long-term functional recovery. Although extensively demonstrated in the preclinical setting, the efficacy of cell-based therapies in stroke patients has been modest at best, if any at all. Translational failure may be due to the ineffective survival and integration of transplanted cells in pro-death stroke microenvironments that are not conducive for the structural reconstruction of damaged brain tissue and repair-related network reorganization. Optimal systemic delivery, timing, cell product, and dose remain open as well. Fortunately, a better understanding of the brain plasticity mechanisms underlying stroke recovery has ushered in a combination approach of cell-based therapy and rehabilitation that is aimed at achieving additive, synergistic, or even maximal beneficial effects. This novel combination therapy is not only targeted at promoting exogenous and endogenous cell survival and augmenting stand-alone restorative mechanisms but also at utilizing rehabilitation to facilitate a graft-host structural and functional integration and plasticity that would effectively remodel stroke tissue and restitute lost functions. This review presents an overview of the combination of cell-based therapy and experimental rehabilitation in stroke models. It also discusses associated shortcomings as well as proposes strategies to address them and help facilitate the advancement of this combination approach.