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Although safety of the grafted cells has been overwhelmingly documented, efficacy has not been forthcoming. Two recently concluded stroke clinical trials on mesenchymal stem cells (MSCs) highlight the importance of strict adherence to the basic science findings of optimal transplant regimen of cell dose, timing, and route of delivery in enhancing the functional outcomes of cell therapy. Echoing the Stem Cell Therapeutics as an Emerging Paradigm for Stroke and Stroke Treatment Academic Industry Roundtable call for an NIH-guided collaborative consortium of multiple laboratories in testing the safety and efficacy of stem cells and their derivatives, not just as stand-alone but preferably in combination with approved thrombolytic or thrombectomy, may further increase the likelihood of successful fruition of translating stem cell therapy for stroke clinical application. The laboratory and clinical experience with MSC therapy for stroke may guide the future translational research on stem cell-based regenerative medicine in neurological disorders. 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