Region-specific brain decellularized extracellular matrix promotes cell recovery in an in vitro model of stroke

Abstract Brain decellularized extracellular matrix (ECM) can be an attractive scaffold capable of mimicking the native ecosystem of the central nervous system tissue. We studied the in vitro response of neural cultures exposed to region-specific brain decellularized ECM scaffolds from three distinct...

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Main Authors: Diego Reginensi, Didio Alberto Ortiz, Bernardino Denis, Solangel Castillo, Andrea Burillo, Nathalie Khoury, Jing Xu, Maria Lucia Dam, Anthony A. Hurtado Escobar, Kunjan R. Dave, Miguel A. Perez-Pinzon, Rolando A. Gittens
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Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-95656-w
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author Diego Reginensi
Didio Alberto Ortiz
Bernardino Denis
Solangel Castillo
Andrea Burillo
Nathalie Khoury
Jing Xu
Maria Lucia Dam
Anthony A. Hurtado Escobar
Kunjan R. Dave
Miguel A. Perez-Pinzon
Rolando A. Gittens
author_facet Diego Reginensi
Didio Alberto Ortiz
Bernardino Denis
Solangel Castillo
Andrea Burillo
Nathalie Khoury
Jing Xu
Maria Lucia Dam
Anthony A. Hurtado Escobar
Kunjan R. Dave
Miguel A. Perez-Pinzon
Rolando A. Gittens
author_sort Diego Reginensi
collection DOAJ
description Abstract Brain decellularized extracellular matrix (ECM) can be an attractive scaffold capable of mimicking the native ecosystem of the central nervous system tissue. We studied the in vitro response of neural cultures exposed to region-specific brain decellularized ECM scaffolds from three distinct neuroanatomical sections: cortex, cerebellum and remaining areas. First, each brain region was evaluated with the isotropic fractionator method to understand the cellular composition of the different cerebral areas. Second, the cerebral regions were subjected to the decellularization process and their respective characterization using molecular, histological, and ultrastructural techniques. Third, the levels of neurotrophic factors in the decellularized brain scaffold were analyzed. Fourth, we studied the region-specific brain decellularized ECM as a mimetic platform for the maturation of PC12 cells, as a unidirectional model of differentiation. Finally, in vitro studies were carried out to evaluate the cell recovery capacity of brain decellularized ECM under stroke-mimetic conditions. Our results show that region-specific brain decellularized ECM can serve as a biomimetic scaffold capable of promoting the growth of neural lineage cells and, in addition, it possesses a combination of structural and biochemical signals (e.g., neurotrophic factors) that are capable of inducing cell phenotypic changes and promote viability and cell recovery in a stroke/ischemia model in vitro.
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spelling doaj-art-4dc54361a7b54b399543b40faefcccf72025-08-20T02:17:05ZengNature PortfolioScientific Reports2045-23222025-04-0115111710.1038/s41598-025-95656-wRegion-specific brain decellularized extracellular matrix promotes cell recovery in an in vitro model of strokeDiego Reginensi0Didio Alberto Ortiz1Bernardino Denis2Solangel Castillo3Andrea Burillo4Nathalie Khoury5Jing Xu6Maria Lucia Dam7Anthony A. Hurtado Escobar8Kunjan R. Dave9Miguel A. Perez-Pinzon10Rolando A. Gittens11Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP)Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP)Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP)Advanced Therapies, School of Medicine, Universidad de Panamá (UP)Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP)Neuroscience Program, University of Miami Miller School of MedicineNeuroscience Program, University of Miami Miller School of MedicineCenter for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP)Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP)Neuroscience Program, University of Miami Miller School of MedicineNeuroscience Program, University of Miami Miller School of MedicineCenter for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP)Abstract Brain decellularized extracellular matrix (ECM) can be an attractive scaffold capable of mimicking the native ecosystem of the central nervous system tissue. We studied the in vitro response of neural cultures exposed to region-specific brain decellularized ECM scaffolds from three distinct neuroanatomical sections: cortex, cerebellum and remaining areas. First, each brain region was evaluated with the isotropic fractionator method to understand the cellular composition of the different cerebral areas. Second, the cerebral regions were subjected to the decellularization process and their respective characterization using molecular, histological, and ultrastructural techniques. Third, the levels of neurotrophic factors in the decellularized brain scaffold were analyzed. Fourth, we studied the region-specific brain decellularized ECM as a mimetic platform for the maturation of PC12 cells, as a unidirectional model of differentiation. Finally, in vitro studies were carried out to evaluate the cell recovery capacity of brain decellularized ECM under stroke-mimetic conditions. Our results show that region-specific brain decellularized ECM can serve as a biomimetic scaffold capable of promoting the growth of neural lineage cells and, in addition, it possesses a combination of structural and biochemical signals (e.g., neurotrophic factors) that are capable of inducing cell phenotypic changes and promote viability and cell recovery in a stroke/ischemia model in vitro.https://doi.org/10.1038/s41598-025-95656-wTissue engineeringDecellularized scaffoldBrain extracellular matrixOxygen-glucose deprivation (OGD).
spellingShingle Diego Reginensi
Didio Alberto Ortiz
Bernardino Denis
Solangel Castillo
Andrea Burillo
Nathalie Khoury
Jing Xu
Maria Lucia Dam
Anthony A. Hurtado Escobar
Kunjan R. Dave
Miguel A. Perez-Pinzon
Rolando A. Gittens
Region-specific brain decellularized extracellular matrix promotes cell recovery in an in vitro model of stroke
Scientific Reports
Tissue engineering
Decellularized scaffold
Brain extracellular matrix
Oxygen-glucose deprivation (OGD).
title Region-specific brain decellularized extracellular matrix promotes cell recovery in an in vitro model of stroke
title_full Region-specific brain decellularized extracellular matrix promotes cell recovery in an in vitro model of stroke
title_fullStr Region-specific brain decellularized extracellular matrix promotes cell recovery in an in vitro model of stroke
title_full_unstemmed Region-specific brain decellularized extracellular matrix promotes cell recovery in an in vitro model of stroke
title_short Region-specific brain decellularized extracellular matrix promotes cell recovery in an in vitro model of stroke
title_sort region specific brain decellularized extracellular matrix promotes cell recovery in an in vitro model of stroke
topic Tissue engineering
Decellularized scaffold
Brain extracellular matrix
Oxygen-glucose deprivation (OGD).
url https://doi.org/10.1038/s41598-025-95656-w
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