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去细胞化人真皮基质作为心脏修复与再生的生物支架

Decellularized Human Dermal Matrix as a Biological Scaffold for Cardiac Repair and Regeneration.

作者信息

Belviso Immacolata, Romano Veronica, Sacco Anna Maria, Ricci Giulia, Massai Diana, Cammarota Marcella, Catizone Angiolina, Schiraldi Chiara, Nurzynska Daria, Terzini Mara, Aldieri Alessandra, Serino Gianpaolo, Schonauer Fabrizio, Sirico Felice, D'Andrea Francesco, Montagnani Stefania, Di Meglio Franca, Castaldo Clotilde

机构信息

Department of Public Health, University of Naples Federico II, Naples, Italy.

Department of Experimental Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy.

出版信息

Front Bioeng Biotechnol. 2020 Mar 20;8:229. doi: 10.3389/fbioe.2020.00229. eCollection 2020.

Abstract

The complex and highly organized environment in which cells reside consists primarily of the extracellular matrix (ECM) that delivers biological signals and physical stimuli to resident cells. In the native myocardium, the ECM contributes to both heart compliance and cardiomyocyte maturation and function. Thus, myocardium regeneration cannot be accomplished if cardiac ECM is not restored. We hypothesize that decellularized human skin might make an easily accessible and viable alternate biological scaffold for cardiac tissue engineering (CTE). To test our hypothesis, we decellularized specimens of both human skin and human myocardium and analyzed and compared their composition by histological methods and quantitative assays. Decellularized dermal matrix was then cut into 600-μm-thick sections and either tested by uniaxial tensile stretching to characterize its mechanical behavior or used as three-dimensional scaffold to assess its capability to support regeneration by resident cardiac progenitor cells (hCPCs) . Histological and quantitative analyses of the dermal matrix provided evidence of both effective decellularization with preserved tissue architecture and retention of ECM proteins and growth factors typical of cardiac matrix. Further, the elastic modulus of the dermal matrix resulted comparable with that reported in literature for the human myocardium and, when tested , dermal matrix resulted a comfortable and protective substrate promoting and supporting hCPC engraftment, survival and cardiomyogenic potential. Our study provides compelling evidence that dermal matrix holds promise as a fully autologous and cost-effective biological scaffold for CTE.

摘要

细胞所处的复杂且高度有序的环境主要由细胞外基质(ECM)构成,细胞外基质向驻留细胞传递生物信号和物理刺激。在天然心肌中,细胞外基质有助于心脏顺应性以及心肌细胞的成熟与功能。因此,如果心脏细胞外基质不能恢复,心肌再生就无法实现。我们假设脱细胞人皮肤可能成为一种易于获取且可行的用于心脏组织工程(CTE)的替代性生物支架。为了验证我们的假设,我们对人皮肤和人心肌标本进行脱细胞处理,并通过组织学方法和定量分析对其成分进行分析和比较。然后将脱细胞真皮基质切成600微米厚的切片,要么通过单轴拉伸试验来表征其力学行为,要么用作三维支架来评估其支持驻留心脏祖细胞(hCPCs)再生的能力。真皮基质的组织学和定量分析提供了有效脱细胞且组织结构得以保留以及保留心脏基质典型的细胞外基质蛋白和生长因子的证据。此外,真皮基质的弹性模量与文献报道的人心肌弹性模量相当,并且在测试时,真皮基质是一种促进和支持hCPC植入、存活及心肌生成潜能的适宜且具有保护作用的基质。我们的研究提供了令人信服的证据,表明真皮基质有望成为一种用于心脏组织工程的完全自体且具有成本效益的生物支架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7a2/7099865/77a7201b8db1/fbioe-08-00229-g001.jpg

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