Multi-faceted effects of mesenchymal stem cells (MSCs) determined by immune microenvironment and their implications on MSC/biomaterial-based inflammatory disease therapy
Multi-faceted effects of mesenchymal stem cells (MSCs) determined by immune microenvironment and their implications on MSC/biomaterial-based inflammatory disease therapy
复制标题
免疫微环境决定间充质干细胞（MSC）的多方面作用及其对基于 MSC/生物材料的炎症性疾病治疗的影响
DOI：
10.1016/j.apmt.2019.100485
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发表时间：
2020-03-01
影响因子：
8.3
通讯作者：
Xiao, Yin
中科院分区：
文献类型：
--
作者：
Chen, Lingling;Liu, Guanqi;Xiao, Yin
炎症性疾病会导致破坏性事件，导致组织丢失和功能障碍。间充质干细胞(MSCs)因其抗炎作用和组织修复的直接作用，常被用作治疗炎性组织损伤的理想实验细胞。尽管有少量的成功报道，但也观察到了有争议的治疗结果，这表明MSCs可能并不总是有益的，并且在炎症性疾病方面具有多方面的功能。我们选择牙髓炎作为疾病模型，观察到人类牙髓炎组织由浸润性巨噬细胞组成，而健康组织主要由牙髓干细胞(DPSCS)组成，牙髓干细胞是MSC的一种。通过体外实验，我们发现脂多糖(LPS)激活的巨噬细胞在促炎症细胞因子IL-6、IL-1β和TNRα的上调下，将DPSCs转化为炎性细胞。其潜在机制与巨噬细胞释放肿瘤坏死因子α导致DPSCS修复能力关闭有关。此外，激活的DPSCs成为促炎调节剂，通过与Wnt5A上调相关的机制增强巨噬细胞的炎症反应。有趣的是，当我们应用一种常用的牙科盖帽材料(IRoot BP Plus)刺激巨噬细胞时，产生的免疫环境抑制了DPSCs的炎症反应，并将其转化为具有高修复能力的抗炎调节剂。这意味着操纵DPSCS的多方面效应对于盖帽材料介导的牙髓炎治疗至关重要。我们的结果共同证明了MSCs在炎症疾病进展过程中的多方面特性：1)修复细胞，2)炎症细胞，3)免疫调节细胞。需要注意的是，MSCs的免疫调节特性并不总是抗炎的；免疫调节特性是由局部免疫环境决定的。在应用细胞/生物材料治疗炎性组织修复和再生时，应考虑MSCs的这种多方面效应。(C)2019爱思唯尔有限公司。保留所有权利。
Inflammatory diseases result in destructive events, leading to tissue loss and functional impairment. Due to their anti-inflammatory effect and direct effect in tissue repair, mesenchymal stem cells (MSCs) are often exploited as ideal experimental cells to cure inflammatory tissue damage. Although a modicum of success has been reported, controversial therapeutic outcomes have also been observed, suggesting that MSCs may not be always beneficial and have multi-faceted functions with respect to inflammatory diseases. We chose dental pulpitis as a disease model and observed that human pulpitis tissue consists of infiltrating macrophages, whereas healthy tissue mainly consists of dental pulp stem cells (DPSCs), a type of MSC population. Through in vitro experiments, we found that lipopolysaccharide (LPS)-activated macrophages turned DPSCs into inflammatory cells with the upregulation of proinflammatory cytokines, IL-6, IL-1 beta, and TNR alpha. The underlying mechanism is related to the release of TNF alpha from macrophages, which led to a shutdown of the reparative capacity of DPSCs. Furthermore, the activated DPSCs became pro-inflammatory regulators, augmenting the inflammation response of macrophages via a mechanism related to the upregulation of WNT5a. Interestingly, when we applied a commonly used dental capping material (iRoot BP plus) to stimulate macrophages, the generated immune environment inhibited the inflammatory response of DPSCs and turned them into anti-inflammatory regulators with a high reparative capacity. This implies that manipulating the multi-faceted effects of DPSCs is vital for capping material-mediated pulpitis treatment. Our results collectively demonstrate the multi-faceted properties of MSCs in the progress of inflammatory disease as 1) reparative cells, 2) inflammatory cells, and 3) immunoregulatory cells. It should be noted that the immunoregulatory property of MSCs is not always anti-inflammatory; the immunoregulatory property is determined by the local immune environment. Such multi-faceted effects of MSCs should be considered when applying cell/biomaterial-based therapies to inflammatory tissue repair and regeneration. (C) 2019 Elsevier Ltd. All rights reserved.