Systemic multipotent adult progenitor cells protect the cerebellum after asphyxia in fetal sheep.

Autor: Gussenhoven R; Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands.; School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands., Ophelders DRMG; Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands.; School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands., Dudink J; Department of Neonatology, Wilhelmina Children's Hospital and Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands., Pieterman K; Biomedical Imaging Group Rotterdam, Department of Radiology and Medical Informatics, Erasmus Medical Centre, Rotterdam, The Netherlands., Lammens M; Department of Pathology, Antwerp University Hospital and University of Antwerp, Edegem, Belgium., Mays RW; Regenerative Medicine, Athersys, Inc., Cleveland, Ohio, USA., Zimmermann LJ; Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands.; School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands., Kramer BW; Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands.; School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.; School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands., Wolfs TGAM; Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands.; School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands., Jellema RK; Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands.
Jazyk: angličtina
Zdroj: Stem cells translational medicine [Stem Cells Transl Med] 2021 Jan; Vol. 10 (1), pp. 57-67. Date of Electronic Publication: 2020 Sep 28.
DOI: 10.1002/sctm.19-0157
Abstrakt: Involvement of the cerebellum in the pathophysiology of hypoxic-ischemic encephalopathy (HIE) in preterm infants is increasingly recognized. We aimed to assess the neuroprotective potential of intravenously administered multipotent adult progenitor cells (MAPCs) in the preterm cerebellum. Instrumented preterm ovine fetuses were subjected to transient global hypoxia-ischemia (HI) by 25 minutes of umbilical cord occlusion at 0.7 of gestation. After reperfusion, two doses of MAPCs were administered intravenously. MAPCs are a plastic adherent bone-marrow-derived population of adult progenitor cells with neuroprotective potency in experimental and clinical studies. Global HI caused marked cortical injury in the cerebellum, histologically indicated by disruption of cortical strata, impeded Purkinje cell development, and decreased dendritic arborization. Furthermore, global HI induced histopathological microgliosis, hypomyelination, and disruption of white matter organization. MAPC treatment significantly prevented cortical injury and region-specifically attenuated white matter injury in the cerebellum following global HI. Diffusion tensor imaging (DTI) detected HI-induced injury and MAPC neuroprotection in the preterm cerebellum. This study has demonstrated in a preclinical large animal model that early systemic MAPC therapy improved structural injury of the preterm cerebellum following global HI. Microstructural improvement was detectable with DTI. These findings support the potential of MAPC therapy for the treatment of HIE and the added clinical value of DTI for the detection of cerebellar injury and the evaluation of cell-based therapy.
(© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)
Databáze: MEDLINE
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