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首页> 外文期刊>Acta biomaterialia >Functional role of glycosaminoglycans in decellularized lung extracellular matrix
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Functional role of glycosaminoglycans in decellularized lung extracellular matrix

机译：糖氨基聚糖在脱细胞肺细胞外基质中的功能作用

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Despite progress in use of decellularized lung scaffolds in ex vivo lung bioengineering schemes, including use of gels and other materials derived from the scaffolds, the detailed composition and functional role of extracellular matrix (ECM) proteoglycans (PGs) and their glycosaminoglycan (GAG) chains remaining in decellularized lungs, is poorly understood. Using a commonly utilized detergent-based decellularization approach in human autopsy lungs resulted in disproportionate losses of GAGs with depletion of chondroitin sulfate/dermatan sulfate (CS/DS) > heparan sulfate (HS) > hyaluronic acid (HA). Specific changes in disaccharide composition of remaining GAGs were observed with disproportionate loss of NS and NS2S for HS groups and of 4S for CS/DS groups. No significant influence of smoking history, sex, time to autopsy, or age was observed in native vs. decellularized lungs. Notably, surface plasmon resonance demonstrated that GAGs remaining in decellularized lungs were unable to bind key matrix-associated growth factors FGF2, HGF, and TGF beta 1. Growth of lung epithelial, pulmonary vascular, and stromal cells cultured on the surface of or embedded within gels derived from decellularized human lungs was differentially and combinatorially enhanced by replenishing specific GAGs and FGF2. HGF, and TGF beta 1. In summary, lung decellularization results in loss and/or dysfunction of specific GAGs or side chains significantly affecting matrix-associated growth factor binding and lung cell metabolism. GAG and matrix-associated growth factor replenishment thus needs to be incorporated into schemes for investigations utilizing gels and other materials produced from decellularized human lungs.
机译：尽管在诸如肺生物工程方案中使用脱细胞肺支架的进展，包括使用凝胶和其他材料衍生自支架，细胞外基质（ECM）蛋白多糖（PGS）及其糖胺聚糖（GAG）链的详细成分和功能作用剩余的茎肺，是较差的理解。使用常用的洗涤剂基脱细胞化方法在人尸检中导致渗损软骨素/皮肤硫酸盐（CS / DS）>硫酸盐（HS）>透明质酸（HA）的渗损损失。通过对HS组的NS和NS2S的不成比例的损失观察到剩余痛苦的二糖组合物的具体变化，并为CS / DS组的4S。在天然与脱细胞肺部，吸烟历史，性别，尸检时间或年龄没有显着影响。值得注意的是，表面等离子体共振表明，贫细胞肺中剩余的GAG不能结合关键的基质相关生长因子FGF2，HGF和TGFβ1。肺上皮，肺血管和在内部表面上培养的基质细胞的生长通过补充特异性的GAG和FGF2，衍生自脱细胞化人肺的凝胶差异，组合增强。 HGF和TGFβ1。总之，肺脱细胞化导致特异性GAG或侧链的损失和/或功能障碍，显着影响基质相关的生长因子结合和肺细胞代谢。因此，需要将GAG和基质相关的生长因子补充掺入利用凝胶和由脱细胞的人肺产生的其他材料的研究方案。

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