Stem cell therapy: A clinical trial of stroke

Bhasin, Ashu; Srivastava, M V Padma; Mohanty, Sujata; Bhatia, Rohit; Kumaran, Senthil; Bose, Shika

doi:10.1016/j.clineuro.2012.10.015

Cited by 144 publications

(120 citation statements)

References 37 publications

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“…Statistically significant improvement was seen in the modified BI at 6 months and in the Laterality index in ipsilateral Broadmann areas 4 and 6 in fMRI at 2 months, but not at 6 months. The same group also published a comparison of the results of the six treated patients and six controls of the BM-MSC group with 14 treated patients and 14 controls of the BM-MNC group [101]. In this study, they also found statistical improvement in modified BI when comparing BM-MNC-treated patients with controls at 6 months, but no longer found improvement in fMRI.…”

Section: Autologous Bm-mncssupporting

confidence: 51%

The Rise of Cell Therapy Trials for Stroke: Review of Published and Registered Studies

Rosado-de-Castro

Pimentel‐Coelho

Fonseca

et al. 2013

Stem Cells and Development

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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.

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Section: Autologous Bm-mncssupporting

confidence: 51%

The Rise of Cell Therapy Trials for Stroke: Review of Published and Registered Studies

Rosado-de-Castro

Pimentel‐Coelho

Fonseca

et al. 2013

Stem Cells and Development

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“…A number of factors support translation to humans, including robustness of preclinical findings across variables such as species studied, species that was the source of the MSCs, time of MSC administration after stroke, and route of administration. Initial experience in small studies of MSCs in humans with stroke has been promising, [45][46][47][48]57 MSCs have an overall excellent safety record in clinical trials of human subjects across numerous diagnoses, [12][13][14]55,56 and MSCs have demonstrated efficacy in nonstroke conditions such as graft versus host disease, where MSCs have been the basis for the first stem cell therapy approved in North America. Overall, the current review suggests utility in further translational studies of MSCs in human patients with ischemic stroke.…”

Section: Resultsmentioning

confidence: 99%

Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke

et al. 2014

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Objectives:To evaluate the quality of preclinical evidence for mesenchymal stromal cell (MSC) treatment of ischemic stroke, determine effect size of MSC therapy, and identify clinical measures that correlate with differences in MSC effects.Methods: A literature search identified studies of MSCs in animal models of cerebral ischemia. For each, a Quality Score was derived, and effect size of MSCs was determined for the most common behavioral and histologic endpoints.Results: Of 46 studies, 44 reported that MSCs significantly improved outcome. The median Quality Score was 5.5 (of 10). The median effect size was 1.78 for modified Neurological Severity Score, 1.73 for the adhesive removal test, 1.02 for the rotarod test, and 0.93 for infarct volume reduction. Quality Score correlated significantly and positively with effect size for the modified Neurological Severity Score. Effect sizes varied significantly with clinical measures such as administration route (intracerebral . intra-arterial . IV, although effect size for IV was nonetheless very large at 1.55) and species receiving MSCs (primate . rat . mouse). Because many MSC mechanisms are restorative, analyses were repeated examining only the 36 preclinical studies administering MSCs $24 hours poststroke; results were overall very similar. Conclusions:In preclinical studies, MSCs have consistently improved multiple outcome measures, with very large effect sizes. Results were robust across species studied, administration route, species of MSC origin, timing, degree of immunogenicity, and dose, and in the presence of comorbidities. In contrast to meta-analyses of preclinical data for other stroke therapies, higher-quality MSC preclinical studies were associated with larger behavioral gains. These findings support the utility of further studies to translate MSCs in the treatment of ischemic stroke in humans.

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“…Clinical trials have already begun with patients with amyotrophic lateral sclerosis, multiple sclerosis, and stroke, with an initial focus on safety. [1][2][3][4][5] Several different types of stem cells have been proposed as therapies, with the basis of their potential benefit ranging from providing nutritive support for injured host tissue, as a reservoir for growth factors, and as replacement neurons for host cells lost to injury or disease. An underlying prerequisite for all of these goals is survival and appropriate localization of the transplanted stem cells.…”

Section: Introductionmentioning

confidence: 99%

Human neural progenitor cells retain viability, phenotype, proliferation, and lineage differentiation when labeled with a novel iron oxide nanoparticle, Molday ION Rhodamine B

Shen¹,

Plachez²,

Chan³

et al. 2013

IJN

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Ultrasmall superparamagnetic iron-oxide particles (USPIOs) loaded into stem cells have been suggested as a way to track stem cell transplantation with magnetic resonance imaging, but the labeling, and post-labeling proliferation, viability, differentiation, and retention of USPIOs within the stem cells have yet to be determined for each type of stem cell and for each type of USPIO. Molday ION Rhodamine B™ (BioPAL, Worcester, MA, USA) (MIRB) has been shown to be a USPIO labeling agent for mesenchymal stem cells, glial progenitor cells, and stem cell lines. In this study, we have evaluated MIRB labeling in human neuroprogenitor cells and found that human neuroprogenitor cells are effectively labeled with MIRB without use of transfection reagents. Viability, proliferation, and differentiation properties are unchanged between MIRB-labeled neuroprogenitors cells and unlabeled cells. Moreover, MIRB-labeled human neuroprogenitor cells can be frozen, thawed, and replated without loss of MIRB or even without loss of their intrinsic biology. Overall, those results show that MIRB has advantageous properties that can be used for cell-based therapy.

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Stem cell therapy: A clinical trial of stroke

Cited by 144 publications

References 37 publications

The Rise of Cell Therapy Trials for Stroke: Review of Published and Registered Studies

The Rise of Cell Therapy Trials for Stroke: Review of Published and Registered Studies

Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke

Human neural progenitor cells retain viability, phenotype, proliferation, and lineage differentiation when labeled with a novel iron oxide nanoparticle, Molday ION Rhodamine B

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