Tissue decellularization by activation of programmed cell death

Tissue decellularization by activation of programmed cell death
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DOI:
10.1016/j.biomaterials.2013.04.058
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发表时间:
2013-08-01
期刊:
影响因子:
14
通讯作者:
Martin, Ivan
Martin, Ivan
中科院分区:
工程技术1区
文献类型:
--
作者:
Bourgine, Paul E.;Pippenger, Benjamin E.;Martin, Ivan

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脱细胞组织,无论是天然的还是工程的,在再生医学领域作为组织和器官修复的支架或植入物正受到越来越多的关注。这种方法提供了在没有免疫匹配要求的情况下提供现成生物活性材料的机会,其基本原理是细胞外基质(ECM)提供的信号可以有效地指导再生。然而,现有的脱细胞方案通常会对来源的ECM造成损害,并且不允许对其结构、生化和/或生物力学特征进行受控保存。在这里,我们建议故意激活程序性细胞死亡作为一种方法,以选择性地靶向组织的细胞成分,从而保持脱细胞ECM的完整性。在工程组织的情况下,该方法可以通过使用(I)永生化细胞系,经工程设计,在暴露于化学诱导剂时经历细胞凋亡,和(Ii)灌流生物反应器系统,支持有效地去除细胞材料来补充。这些工具的结合可能导致更合适的材料的简化开发,基于工程和去细胞的ECM,并包括一套专门设计用于激活内源性再生过程的定制信号。(C)2013爱思唯尔有限公司。保留所有权利。
Decellularized tissues, native or engineered, are receiving increasing interest in the field of regenerative medicine as scaffolds or implants for tissue and organ repair. The approach, which offers the opportunity to deliver off-the-shelf bioactive materials without immuno-matching requirements, is based on the rationale that extracellular matrix (ECM)-presented cues can be potently instructive towards regeneration. However, existing decellularization protocols typically result in damage to the source ECM and do not allow the controlled preservation of its structural, biochemical and/or biomechanical features. Here we propose the deliberate activation of programmed cell death as a method to selectively target the cellular component of a tissue and thereby to preserve the integrity of the decellularized ECM. In the case of engineered tissues, the approach could be complemented by the use of (i) an immortalized cell line, engineered to undergo apoptosis upon exposure to a chemical inducer, and (ii) a perfusion bioreactor system, supporting efficient removal of cellular material. The combination of these tools may lead to the streamlined development of more appropriate materials, based on engineered and decellularized ECM and including a customized set of signals specifically designed to activate endogenous regenerative processes. (C) 2013 Elsevier Ltd. All rights reserved.