Stroke is the second leading cause of death worldwide and the most common cause of severe disability. Neuroprotection and repair mechanisms supporting endogenous brain plasticity are often insufficient to allow complete recovery. While numerous neuroprotective drugs trials have failed to demonstrate benefits for patients, they have provided interesting translational research lessons related to neurorestorative therapy mechanisms in stroke. Stroke damage is not limited to neurons but involve all brain cell type including the extracellular matrix in a “glio-neurovascular niche”. Targeting a range of host brain cells, biotherapies such as growth factors and therapeutic cells, currently hold great promise as a regenerative medical strategy for stroke. These techniques can promote both neuroprotection and delayed neural repair through neuro-synaptogenesis, angiogenesis, oligodendrogliogenesis, axonal sprouting and immunomodulatory effects. Their complex mechanisms of action are interdependent and vary according to the particular growth factor or grafted cell type. For example, while “peripheral” stem or stromal cells can provide paracrine trophic support, neural stem/progenitor cells (NSC) or mature neurons can act as more direct neural replacements. With a wide therapeutic time window after stroke, biotherapies could be used to treat many patients. However, guidelines for selecting the optimal time window, and the best delivery routes and doses are still debated and the answers may depend on the chosen product and its expected mechanism including early neuroprotection, delayed neural repair, trophic systemic transient effects or graft survival and integration. Currently, the great variety of growth factors, cell sources and cell therapy products form a therapeutic arsenal that is available for stroke treatment. Their effective clinical use will require prior careful considerations regarding safety (e.g. tumorgenicity, immunogenicity), potential efficacy, cell characterization, delivery route and in vivo biodistribution. Bone marrow-derived cell populations such as mesenchymal stromal/stem cells (MSC) or mononuclear cells (MNC), umbilical cord stem cells and NSC are most investigated notably in clinical trials. Finally, we discuss perspectives concerning potential novel biotherapies such as combinatorial approaches (growth factor combined with cell therapy, in vitro optimization of cell products, or co-transplantation) and the development of biomaterials, which could be used as injectable hydrogel scaffold matrices that could protect a cell graft or selectively deliver drugs and growth factors into the post-stroke cavity at chronic stages. Considering the remaining questions about the best procedure and the safety cautions, we can hope that future translational research about biotherapies will bring more efficient treatments that will decrease post-stroke disability for many patients.

Les accidents vasculaires cérébraux (AVC) représentent la seconde cause de mortalité et la première cause de handicap. En améliorant la neuroprotection et la plasticité endogènes, fréquemment insuffisantes pour assurer une récupération complète, les biothérapies semblent très prometteuses. Leurs mécanismes d’action dépendent du facteur de croissance ou des cellules choisis. On peut distinguer un effet neurotrophique paracrine pour les cellules souches « périphériques » et un effet de remplacement cellulaire plus direct pour les cellules souches neurales (NSC). Cependant, les délais, les doses et les voies d’administration restent débattus. Parmi les nombreuses cellules disponibles, les cellules de la moelle osseuse ou du cordon (par ex : cellules souches/stromales mésenchymateuses, ou cellules mononucléées) et les NSC sont les plus étudiées. En perspective, nous discutons ici les thérapies combinées (facteur de croissance et cellules, co-transplantations…) et l’utilisation de biomatériaux (hydrogels injectables) libérant l’agent thérapeutique ou protégeant le greffon. En tenant compte des questions en suspens sur la meilleure procédure et la sécurité (par ex : tumorigénicité, immunogénicité), nous pouvons espérer que les biothérapies deviennent une stratégie thérapeutique efficace, avec une large fenêtre thérapeutique, pour réduire le handicap post-AVC de nombreux patients.