Mapping the acute time course of immune cell infiltration into an ECM hydrogel in a rat model of stroke using 19 F MRI.
Autor: | Modo M; University of Pittsburgh, McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA; University of Pittsburgh, Department of Radiology, Pittsburgh, PA, USA; University of Pittsburgh, Department of Bioengineering, Pittsburgh, PA, USA. Electronic address: mmm154@pitt.edu., Ghuman H; University of Pittsburgh, McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA; University of Pittsburgh, Department of Bioengineering, Pittsburgh, PA, USA., Azar R; University of Pittsburgh, Department of Bioengineering, Pittsburgh, PA, USA., Krafty R; University of Pittsburgh, Department of Biological Sciences, Pittsburgh, PA, USA., Badylak SF; University of Pittsburgh, McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA; University of Pittsburgh, Department of Surgery, Pittsburgh, PA, USA., Hitchens TK; University of Pittsburgh, Department of Neurobiology, Pittsburgh, PA, USA. |
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Jazyk: | angličtina |
Zdroj: | Biomaterials [Biomaterials] 2022 Mar; Vol. 282, pp. 121386. Date of Electronic Publication: 2022 Jan 25. |
DOI: | 10.1016/j.biomaterials.2022.121386 |
Abstrakt: | Extracellular matrix (ECM) hydrogel implantation into a stroke-induced tissue cavity invokes a robust cellular immune response. However, the spatio-temporal dynamics of immune cell infiltration into peri-infarct brain tissues versus the ECM-bioscaffold remain poorly understood. We here tagged peripheral immune cells using perfluorocarbon (PFC) nanoemulsions that afford their visualization by 19 F magnetic resonance imaging (MRI). Prior to ECM hydrogel implantation, only blood vessels could be detected using 19 F MRI. Using "time-lapse" 19 F MRI, we established the infiltration of immune cells into the peri-infarct area occurs 5-6 h post-ECM implantation. Immune cells also infiltrated through the stump of the MCA, as well as a hydrogel bridge that formed between the tissue cavity and the burr hole in the skull. Tissue-based migration into the bioscaffold was observed between 9 and 12 h with a peak signal measured between 12 and 18 h post-implantation. Fluorescence-activated cell sorting of circulating immune cells revealed that 9% of cells were labeled with PFC nanoemulsions, of which the vast majority were neutrophils (40%) or monocytes (48%). Histology at 24 h post-implantation, in contrast, indicated that macrophages (35%) were more numerous in the peri-infarct area than neutrophils (11%), whereas the vast majority of immune cells within the ECM hydrogel were neutrophils (66%). Only a small fraction (12%) of immune cells did not contain PFC nanoemulsions, indicating a low type II error for 19 F MRI. 19 F MRI hence provides a unique tool to improve our understanding of the spatio-temporal dynamics of immune cells invading bioscaffolds and effecting biodegradation. (Copyright © 2022 Elsevier Ltd. All rights reserved.) |
Databáze: | MEDLINE |
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