Blood-based biomarkers and stem cell therapy in human stroke: a systematic review
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REVIEW
Blood‑based biomarkers and stem cell therapy in human stroke: a systematic review Elena Palà1 · Alejandro Bustamante1 · Jukka Jolkkonen2,3 · Marc Hommel4 · Anna Rosell1 · Joan Montaner1,5 Received: 25 March 2020 / Accepted: 26 June 2020 © Springer Nature B.V. 2020
Abstract Stroke is one of the main causes of death and disability worldwide. Cell therapy represents a promising therapeutic approach to improve stroke outcome. Measurement of blood-based biomarkers might serve as a proof-of-concept to monitor the mechanisms undergirding these treatments, and such compounds could be used as surrogate biomarkers to monitor the safety and efficacy of cell therapies in the future. Additionally, the measurement of biomarkers that correlate with circulating stem cells in observational studies might be of interest to improve the understanding of how these cells are spontaneously mobilized and carry out their action after stroke. Thus, a systematic review has been herein performed on blood-based biomarkers assessed in stroke patients treated with cell therapy or in observational studies in which circulating stem cells have been measured after stroke. Keywords Stroke · Stem cells · Endothelial progenitor cells · Biomarker · Cell therapy
Introduction Stroke is one of the main causes of death and disability worldwide [1]. Stoke is classified as hemorrhagic (due to a blood vessel rupture), or ischemic (due to a vascular occlusion), the latter constituting 80–85% of all strokes. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05627-9) contains supplementary material, which is available to authorized users. * Alejandro Bustamante [email protected] 1
Neurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Pg. Vall d’Hebron, 119‑129. Hospital Universitari Vall d’Hebron, 08035 Barcelona, Spain
2
Department of Neurology, Institute of Clinical Medicine, University of Eastern, Kuopio, Finland
3
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
4
AGEIS EA 7407, University Grenoble Alpes, Grenoble, France
5
Institute de Biomedicine of SevilleIBiS/Hospital Unive Virgen del Rocío/CSIC/University of Seville & Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain
Following stroke, reduced blood flow triggers a complex chain of events that lead to irreversible tissue injury and cell death [2]. On the other hand, after stroke, an endogenous regenerative response is activated, including angiogenesis, neurogenesis, gliogenesis and remyelination among other processes, demonstrating the plastic nature of the brain. At the peripheral level, brain injury induces, among other processes, the mobilization of endothelial progenitor cells (EPCs), which enhance poststroke neurorepair by two main mechanisms. The first is the incorporation of the cells in the new blood vessels during vascular remodeling. The second is an indirect me
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