Transplantation of autologous bone marrow mononuclear cells (BMMCs) has been proven safe in animal and human studies. However, there are very few studies in stroke patients. In this study, intra-arterial autologous BMMCs were infused in patients with moderate to severe acute middle cerebral artery infarcts. The subjects of this study included 20 patients with early or late spontaneous recanalization but with persistent deficits, in whom treatment could be initiated between 3 and 7 days after stroke onset. Mononuclear cells were isolated from bone marrow aspirates and infused at the proximal middle cerebral artery of the affected hemisphere. Safety analysis (primary endpoint) during the 6-month follow-up assessed death, any serious clinical events, neurological worsening with ≥ 4-point increase in National Institutes of Health Stroke Scale (NIHSS) scores, seizures, epileptogenic activity on electroencephalogram, and neuroimaging complications including new ischemic, hemorrhagic, or neoplastic lesions. Satisfactory clinical improvement (secondary endpoint) at 90 days was defined according to the pretreatment NIHSS scores as follows: modified Rankin Scale score of 0 in patients with NIHSS 14. Good clinical outcome was defined as mRS ≤2 at 90 days. Serial clinical, laboratory, electroencephalogram, and imaging evaluations showed no procedure-related adverse events. Satisfactory clinical improvement occurred in 6/20 (30%) patients at 90 days. Eight patients (40%) showed a good clinical outcome. Infusion of intra-arterial autologous BMMCs appears to be safe in patients with moderate to severe acute middle cerebral artery strokes. No cases of intrahospital mortality were seen in this pilot trial. Larger prospective randomized trials are warranted to assess the efficacy of this treatment approach.

To assess the safety and feasibility of intra-arterial transplantation of autologous bone marrow mononuclear cells in patients with middle cerebral artery ischemic stroke within 90 days of symptom onset. Six patients were included in the study, and they received 1-5 × 10(8) bone marrow mononuclear cell and were evaluated using blood tests, neurological and imaging examination before treatment, and 1, 3, 7, 30, 60, 90, 120 and 180 days after transplantation. Scintigraphies were carried out 2 and 24 h after the procedure to analyze the biodistribution of labeled cells. Electroencephalogram was conducted within 7 days after transplantation. No patients exhibited any complication or adverse events during the procedure. There was no worsening in the neurological scales until the end of the follow-up. Intra-arterial bone marrow mononuclear cell transplantation is feasible and safe in patients with nonacute ischemic strokes of the middle cerebral artery. Further studies are required to evaluate the efficacy of this therapy.

To assess the biodistribution of bone marrow mononuclear cells (BMMNC) delivered by different routes in patients with subacute middle cerebral artery ischemic stroke. This was a nonrandomized, open-label Phase I clinical trial. After bone marrow harvesting, BMMNCs were labeled with technetium-99m and intra-arterially or intravenously delivered together with the unlabeled cells. Scintigraphies were carried out at 2 and 24 h after cell transplantation. Clinical follow-up was continued for 6 months. Twelve patients were included, between 19 and 89 days after stroke, and received 1-5 × 10(8) BMMNCs. The intra-arterial group had greater radioactive counts in the liver and spleen and lower counts in the lungs at 2 and 24 h, while in the brain they were low and similar for both routes. BMMNC labeling with technetium-99m allowed imaging for up to 24 h after intra-arterial or intravenous injection in stroke patients.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been used for diagnoses in biomedical applications, due to their unique properties and their apparent safety for humans. In general, SPIONs do not seem to produce cell damage, although their long-term in vivo effects continue to be investigated. The possibility of efficiently labeling cells with these magnetic nanoparticles has stimulated their use to noninvasively track cells by magnetic resonance imaging after transplantation. SPIONs are attracting increasing attention and are one of the preferred methods for cell labeling and tracking in preclinical and clinical studies. For clinical protocol approval of magnetic-labeled cell tracking, it is essential to expand our knowledge of the time course of SPIONs after cell incorporation and transplantation. This review focuses on the recent advances in tracking SPION-labeled stem cells, analyzing the possibilities and limitations of their use, not only focusing on myocardial infarction but also discussing other models.

Stroke is the second leading cause of death and the third leading cause of disability worldwide. Approximately 16 million first-ever strokes occur each year, leading to nearly 6 million deaths. Nevertheless, currently, very few therapeutic options are available. Cell therapies have been applied successfully in different hematological diseases, and are currently being investigated for treating ischemic heart disease, with promising results. Recent preclinical studies have indicated that cell therapies may provide structural and functional benefits after stroke. However, the effects of these treatments are not yet fully understood and are the subject of continuing investigation. Meanwhile, different clinical trials for stroke, the majority of them small, nonrandomized, and uncontrolled, have been reported, and their results indicate that cell therapy seems safe and feasible in these conditions. In the last 2 years, the number of published and registered trials has dramatically increased. Here, we review the main findings available in the field, with emphasis on the clinical results. Moreover, we address some of the questions that have been raised to date, to improve future studies.