The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study
The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study
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DOI：
10.1111/wrr.12526
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发表时间：
2017-03-01
影响因子：
2.9
通讯作者：
Nuutila, Kristo
中科院分区：
文献类型：
--
作者：
Kruse, Carla R.;Singh, Mansher;Nuutila, Kristo
创面微环境在创面愈合过程中起着重要作用。它包含了参与伤口病理生理学的各种外部和内部因素。pH值是影响伤口愈合的重要因素，在整个愈合过程中不断变化。先前的几项研究已经调查了pH值与病原体的关系，但集中于pH值对伤口愈合本身的影响的研究是不确定的。本研究的目的是通过研究pH对体外人原代角质形成细胞和成纤维细胞功能以及对体内伤口愈合的影响，全面并以受控方式研究pH对伤口愈合的影响。在体外，原代人角质形成细胞和成纤维细胞培养在不同水平的pH值（5.5-12.5）和细胞活力，增殖和迁移的影响进行了研究。采用大鼠全层创伤模型，研究pH（5.5-9.5）对体内创伤愈合的影响。通过测量来自暴露于不同pH环境的伤口和细胞培养物的IL-1 α浓度来监测pH对炎症的影响。我们的研究结果表明，这两种皮肤细胞类型耐受广泛的pH值非常好。他们进一步证明，与中性环境相比，酸性和碱性环境都减缓了细胞迁移，有趣的是碱性条件显著增强了细胞增殖。体内实验的结果表明，长时间的强酸性伤口环境会阻止伤口闭合和上皮再生，而长时间的碱性环境对伤口闭合或上皮再生没有任何负面影响。另外，体外和体内研究均表明，长时间的酸性条件显著增加成纤维细胞培养物和伤口液中IL-1的表达，而长时间的碱性条件不会导致IL-1 α的量升高。
Wound microenvironment plays a major role in the process of wound healing. It contains various external and internal factors that participate in wound pathophysiology. The pH is an important factor that influences wound healing by changing throughout the healing process. Several previous studies have investigated the role of pH in relation to pathogens but studies concentrating on the effects of pH on wound healing itself are inconclusive. The purpose of this study was to comprehensively and in a controlled fashion investigate the effect of pH on wound healing by studying its effect on human primary keratinocyte and fibroblast function in vitro and on wound healing in vivo. In vitro, primary human keratinocytes and fibroblasts were cultured in different levels of pH (5.5-12.5) and the effect on cell viability, proliferation, and migration was studied. A rat full-thickness wound model was used to investigate the effect of pH (5.5-9.5) on wound healing in vivo. The effect of pH on inflammation was monitored by measuring IL-1 alpha concentrations from wounds and cell cultures exposed to different pH environments. Our results showed that both skin cell types tolerated wide range of pH very well. They further demonstrated that both acidic and alkaline environments decelerated cell migration in comparison to neutral environments and interestingly alkaline conditions significantly enhanced cell proliferation. Results from the in vivo experiments indicated that a prolonged, strongly acidic wound environment prevents both wound closure and reepithelialization while a prolonged alkaline environment did not have any negative impact on wound closure or reepithelialization. Separately, both in vitro and in vivo studies showed that prolonged acidic conditions significantly increased the expression of IL-1 in fibroblast cultures and in wound fluid, whereas prolonged alkaline conditions did not result in elevated amounts of IL-1 alpha.