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Review of Preclinical and Clinical Studies of Bone Marrow-Derived Cell Therapies for Intracerebral Hemorrhage.

ABSTRACT: Stroke is the second leading cause of mortality worldwide, causing millions of deaths annually, and is also a major cause of disability-adjusted life years. Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a fatality rate of about 50% in the first 30 days, with limited treatment possibilities. In the past two decades, the therapeutic potential of bone marrow-derived cells (particularly mesenchymal stem cells and mononuclear cells) has been intensively investigated in preclinical models of different neurological diseases, including models of intracerebral hemorrhage and subarachnoid hemorrhage. More recently, clinical studies, most of them small, unblinded, and nonrandomized, have suggested that the therapy with bone marrow-derived cells is safe and feasible in patients with ischemic or hemorrhagic stroke. This review discusses the available evidence on the use of bone marrow-derived cells to treat hemorrhagic strokes. Distinctive properties of animal studies are analyzed, including study design, cell dose, administration route, therapeutic time window, and possible mechanisms of action. Furthermore, clinical trials are also reviewed and discussed, with the objective of improving future studies in the field.

SUBMITTER: Rosado-de-Castro PH

PROVIDER: S-EPMC5028871 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Review of Preclinical and Clinical Studies of Bone Marrow-Derived Cell Therapies for Intracerebral Hemorrhage.

Rosado-de-Castro Paulo Henrique PH de Carvalho Felipe Gonçalves FG de Freitas Gabriel Rodriguez GR Mendez-Otero Rosalia R Pimentel-Coelho Pedro Moreno PM

Stem cells international 20160906

Stroke is the second leading cause of mortality worldwide, causing millions of deaths annually, and is also a major cause of disability-adjusted life years. Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a fatality rate of about 50% in the first 30 days, with limited treatment possibilities. In the past two decades, the therapeutic potential of bone marrow-derived cells (particularly mesenchymal stem cells and mononuclear cells) has been intensively investigated in ...[more]

PMID: 27698671

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Project description:BackgroundApproximately half of patients with spontaneous intracerebral hemorrhage (ICH) die within 1 year. Prognostication in this context is of great importance, to guide goals of care discussions, clinical decision-making, and risk stratification. However, available prognostic scores are hardly used in clinical practice. The purpose of this review article is to identify existing outcome prediction scores for spontaneous intracerebral hemorrhage (ICH) discuss their shortcomings, and to suggest how to create and validate more useful scores.Main textThrough a literature review this article identifies existing ICH outcome prediction models. Using the Essen-ICH-score as an example, we demonstrate a complete score validation including discrimination, calibration and net benefit calculations. Score performance is illustrated in the Erlangen UKER-ICH-cohort (NCT03183167). We identified 19 prediction scores, half of which used mortality as endpoint, the remainder used disability, typically the dichotomized modified Rankin score assessed at variable time points after the index ICH. Complete score validation by our criteria was only available for the max-ICH score. Our validation of the Essen-ICH-score regarding prediction of unfavorable outcome showed good discrimination (area under the curve 0.87), fair calibration (calibration intercept 1.0, slope 0.84), and an overall net benefit of using the score as a decision tool. We discuss methodological pitfalls of prediction scores, e.g. the withdrawal of care (WOC) bias, physiological predictor variables that are often neglected by authors of clinical scores, and incomplete score validation. Future scores need to integrate new predictor variables, patient-reported outcome measures, and reduce the WOC bias. Validation needs to be standardized and thorough. Lastly, we discuss the integration of current ICH scoring systems in clinical practice with the awareness of their shortcomings.ConclusionPresently available prognostic scores for ICH do not fulfill essential quality standards. Novel prognostic scores need to be developed to inform the design of research studies and improve clinical care in patients with ICH.

Dataset Information

Review of Preclinical and Clinical Studies of Bone Marrow-Derived Cell Therapies for Intracerebral Hemorrhage.

Publications

Review of Preclinical and Clinical Studies of Bone Marrow-Derived Cell Therapies for Intracerebral Hemorrhage.

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