Cell Therapy and Functional Recovery of Stroke.

Stroke is the most common cause of disability. Brain repair mechanisms are often insufficient to allow a full recovery. Stroke damage involve all brain cell type and extracellular matrix which represent the crucial "glio-neurovascular niche" useful for brain plasticity. Regenerative medicine including cell therapies hold great promise to decrease post-stroke disability of many patients, by promoting both neuroprotection and neural repair through direct effects on brain lesion and/or systemic effects such as immunomodulation. Mechanisms of action vary according to each grafted cell type: "peripheral" stem cells, such as mesenchymal stem cells (MSC), can provide paracrine trophic support, and neural stem/progenitor cells (NSC) or neurons can act as direct cells' replacements. Optimal time window, route, and doses are still debated, and may depend on the chosen medicinal product and its expected mechanism such as neuroprotection, delayed brain repair, systemic effects, or graft survival and integration in host network. MSC, mononuclear cells (MNC), umbilical cord stem cells and NSC are the most investigated. Innovative approaches are implemented concerning combinatorial approaches with growth factors and biomaterials such as injectable hydrogels which could protect a cell graft and/or deliver drugs into the post-stroke cavity at chronic stages. Through main publications of the last two decades, we provide in this review concepts and suggestions to improve future translational researches and larger clinical trials of cell therapy in stroke.