title: Intravenously Transplanted Human Bone Marrow Endothelial Progenitor Cells Engraft Within Brain Capillaries, Preserve Mitochondrial Morphology, and Display Pinocytotic Activity Toward Blood-Brain Barrier Repair in Ischemic Stroke Rats.
abstract: Stroke is a life-threatening disease with limited therapeutic options. Cell therapy has emerged as an experimental stroke treatment. Blood-brain barrier (BBB) impairment is a key pathological manifestation of ischemic stroke, and barrier repair is an innovative target for neurorestoration in stroke. Here, we evaluated via electron microscopy the ability of transplanted human bone marrow endothelial progenitor cells (hBMEPCs) to repair the BBB in adult Sprague-Dawley rats subjected to transient middle cerebral artery occlusion (tMCAO). β-galactosidase prelabeled hBMEPCs were intravenously transplanted 48 hours post-tMCAO. Ultrastructural analysis of microvessels in nontransplant stroke rats revealed typical BBB pathology. At 5 days post-transplantation with hBMEPCs, stroke rats displayed widespread vascular repair in bilateral striatum and motor cortex, characterized by robust cell engraftment within capillaries. hBMEPC transplanted stroke rats exhibited near normal morphology of endothelial cells (ECs), pericytes, and astrocytes, without detectable perivascular edema. Near normal morphology of mitochondria was also detected in ECs and perivascular astrocytes from transplanted stroke rats. Equally notable, we observed numerous pinocytic vesicles within engrafted cells. Robust engraftment and intricate functionality of transplanted hBMEPCs likely abrogated stroke-altered vasculature. Preserving mitochondria and augmenting pinocytosis in cell-based therapeutics represent a new neurorestorative mechanism in BBB repair for stroke. Stem Cells 2017;35:1246-1258.
authors.affiliation: Center of Excellence for Aging & Brain Repair.|Department of Neurosurgery and Brain Repair.|Department of Molecular Pharmacology and Physiology.|Department of Pathology and Cell Biology, Morsani College of Medicine.
authors.forename: Svitlana
authors.initials: S
authors.lastname: Garbuzova-Davis
authors.affiliation: Department of Integrative Biology, University of South Florida, Tampa, Florida, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Haller
authors.affiliation: Center of Excellence for Aging & Brain Repair.
authors.forename: Roger
authors.initials: R
authors.lastname: Lin
authors.affiliation: Center of Excellence for Aging & Brain Repair.|Department of Neurosurgery and Brain Repair.
authors.forename: Cesario V
authors.initials: CV
authors.lastname: Borlongan
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000648:ultrastructure; D016026:Bone Marrow Transplantation; D002545:Brain Ischemia / Q000150:complications / Q000628:therapy*; D002196:Capillaries / Q000473:pathology* / Q000648:ultrastructure; D002469:Cell Separation; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000637:transplantation*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D010873:Pinocytosis; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000150:complications / Q000628:therapy*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase
keywords: Blood-brain barrier; Electron microscopy; Human bone marrow endothelial progenitor cells; Middle cerebral artery occlusion; Rats; Repair