Challenges in developing a reseeded, tissue-engineered aortic valve prosthesis.

Challenges in developing a reseeded, tissue-engineered aortic valve prosthesis.
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开发重新种植的组织工程主动脉瓣假体面临的挑战

DOI:
10.1093/ejcts/ezw057
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发表时间:
2016
期刊:
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
影响因子:
--
通讯作者:
Akhyari P
Akhyari P
中科院分区:
--
文献类型:
--
作者:
Raschke S;Baier K;Nehrenheim L;Selig JI;Schomaker M;Lichtenberg A;Meyer H;Akhyari P

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目的生物心脏瓣膜置换术由于植入后的退变过程,其耐用性有限。组织工程学可能为开发优化的瓣膜移植物提供新的途径。尽管去细胞心脏瓣膜的再内皮化已经成功实施,但间质再生仍然是一个未实现的目标,尽管它对于瓣膜的功能和再生潜力是必不可少的。这项研究的目的是比较不同的概念,以改善脱细胞心脏瓣膜的体外间质再充填。为了研究瓣膜间质细胞(VIC)在生理环境中的细胞行为,评价无细胞瓣膜在体外培养群中的潜力,建立了一种新的心脏瓣膜三维模型。方法用洗涤剂溶液脱去主动脉瓣细胞,并用胰酶或激光穿孔处理。随后,用补种装置在脱细胞的细胞外基质(DECM)中重新接种绵羊VIC,以在受控条件下在限定的区域内提供基质的再填充。在VIC最初附着后,重新种植的dECM被转移到Transwell系统中,以改善瓣膜基质内的营养供应。组织学分析细胞迁移和细胞标志物的表达。结果SVIC不能迁移到未经处理的dECM基质中,激光穿孔dECM中重新种植的结果不一致。然而,胰酶消化增加了瓣膜尖部对VIC穿透和浅表区域再充填的敏感性。此外,在转井系统中种植补种的dECM显著增加了重新填充瓣膜基质的细胞总数和它们的平均迁移距离,代表了最佳的再填充结果。免疫组织化学分析和原位酶谱分析显示,培养7d后VIC的再生处于低激活状态。结论比较不同方法增加洗涤剂DECM的间质再生,附加有限的胰酶处理是最有效的。然而,脱细胞心脏瓣膜的完全间质再生仍然是一项具有挑战性的努力。额外的实验微调可能会改善心脏瓣膜组织工程的体外结果。
OBJECTIVESBiological heart valve prostheses are characterized by a limited durability due to the degenerative processes after implantation. Tissue engineering may provide new approaches in the development of optimized valvular grafts. While re-endothelialization of decellularized heart valves has already been successfully implemented, interstitial repopulation still remains an unaccomplished objective although it is essential for valvular functionality and regeneration potential. The aim of this study was to compare different concepts for an improvedin vitrointerstitial repopulation of decellularized heart valves. A novel 3D heart valve model has been developed to investigate the cell behaviour of valvular interstitial cells (VIC) in their physiological environment and to evaluate the potential ofin vitrorepopulation of acellular heart valves.METHODSOvine aortic heart valves were decellularized by detergent solutions and additionally treated with trypsin or laser perforation. Subsequently, the decellularized extracellular matrices (dECM) were reseeded with ovine VIC using reseeding devices to provide a repopulation of the matrix on a defined area under controlled conditions. After an initial attachment of the VIC, reseeded dECM were transferred into a transwell system to improve the nutrient supply inside the valvular matrix. Cell migration and expression of cell markers were analysed histologically. The results were compared with VIC cultivation in a biological scaffold.RESULTSVIC did not migrate into the matrix of untreated dECM and reseeding in laser perforated dECM showed inconsistent results. However, trypsinization increased the susceptibility of the valvular cusps to VIC penetration and repopulation of superficial areas. Additionally, the cultivation of reseeded dECM in a transwell system significantly increased the total number of cells repopulating the valvular matrix and their mean migration distance, representing the best repopulation results. Immunohistological analysis andin situzymography revealed a low activation status of repopulating VIC after 7 days of culture.CONCLUSIONSA comparison of different techniques for increasing interstitial repopulation of detergent dECM revealed that an additional limited trypsin treatment was most effective. Nevertheless, a complete interstitial repopulation of decellularized heart valves remains a challenging endeavour. Additional experimental fine-tuning may improve thein vitroresults of heart valve tissue engineering.
DOI: 10.1088/1478-3975/6/3/036004
发表时间: 2009-09-01
期刊: PHYSICAL BIOLOGY
影响因子: 2
作者:
Ma, Xiaoyan;Lynch, Holley E.;Hutson, M. Shane
通讯作者: Hutson, M. Shane
DOI: 10.1161/circulationaha.109.926873
发表时间: 2010-09-14
期刊: CIRCULATION
影响因子: 37.8
作者:
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DOI: --
发表时间: 2014
影响因子: 3.3
作者:
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DOI: --
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DOI: --
发表时间: 2002
期刊:
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