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区域特异性脑脱细胞细胞外基质在中风体外模型中促进细胞恢复。

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

作者信息

Reginensi Diego, Ortiz Didio Alberto, Denis Bernardino, Castillo Solangel, Burillo Andrea, Khoury Nathalie, Xu Jing, Dam Maria Lucia, Escobar Anthony A Hurtado, Dave Kunjan R, Perez-Pinzon Miguel A, Gittens Rolando A

机构信息

Center for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Panama, Panama.

Advanced Therapies, School of Medicine, Universidad de Panamá (UP), Panama, Panama.

出版信息

Sci Rep. 2025 Apr 7;15(1):11921. doi: 10.1038/s41598-025-95656-w.

DOI:10.1038/s41598-025-95656-w
PMID:40195414
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11976941/
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.

摘要

脑脱细胞细胞外基质(ECM)可以成为一种有吸引力的支架,能够模拟中枢神经系统组织的天然生态系统。我们研究了暴露于来自三个不同神经解剖学区域(皮质、小脑和其余区域)的区域特异性脑脱细胞ECM支架的神经培养物的体外反应。首先,使用各向同性分离法评估每个脑区,以了解不同脑区的细胞组成。其次,对脑区进行脱细胞处理,并使用分子、组织学和超微结构技术对其进行各自的表征。第三,分析脱细胞脑支架中神经营养因子的水平。第四,我们研究了区域特异性脑脱细胞ECM作为PC12细胞成熟的模拟平台,作为一种单向分化模型。最后,进行体外研究以评估在模拟中风条件下脑脱细胞ECM的细胞恢复能力。我们的结果表明,区域特异性脑脱细胞ECM可以作为一种仿生支架,能够促进神经谱系细胞的生长,此外,它还具有结构和生化信号(如神经营养因子)的组合,能够在体外中风/缺血模型中诱导细胞表型变化并促进细胞活力和细胞恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/0b0e3ce59b8d/41598_2025_95656_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/c70d1d2ba17c/41598_2025_95656_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/a3a1864398ef/41598_2025_95656_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/3a1632791fa7/41598_2025_95656_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/d130c7fc75cd/41598_2025_95656_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/0b0e3ce59b8d/41598_2025_95656_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/c70d1d2ba17c/41598_2025_95656_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/a3a1864398ef/41598_2025_95656_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/3a1632791fa7/41598_2025_95656_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/d130c7fc75cd/41598_2025_95656_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c96/11976941/0b0e3ce59b8d/41598_2025_95656_Fig5_HTML.jpg

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