Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam 13494, Korea.
Int J Mol Sci. 2019 Sep 27;20(19):4815. doi: 10.3390/ijms20194815.
Bronchopulmonary dysplasia (BPD), caused by hyperoxia in newborns and infants, results in lung damage and abnormal pulmonary function. However, the current treatments for BPD are steroidal and pharmacological therapies, which cause neurodevelopmental impairment. Treatment with umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) is an efficient alternative approach. To prevent pulmonary inflammation in BPD, this study investigated the hypothesis that a key regulator was secreted by MSCs to polarize inflammatory macrophages into anti-inflammatory macrophages at inflammation sites. Lipopolysaccharide-induced macrophages co-cultured with MSCs secreted low levels of the inflammatory cytokines, IL-8 and IL-6, but high levels of the anti-inflammatory cytokine, IL-10. Silencing decorin in MSCs suppressed the expression of CD44, which mediates anti-inflammatory activity in macrophages. The effects of MSCs were examined in a rat model of hyperoxic lung damage. Macrophage polarization differed depending on the levels of decorin secreted by MSCs. Moreover, intratracheal injection of decorin-silenced MSCs or MSCs secreting low levels of decorin confirmed impaired alveolarization of damaged lung tissues by down-regulation of decorin. In tissues, a decrease in the anti-inflammatory macrophage marker, CD163, was observed via CD44. Thus, we identified decorin as a key paracrine factor, inducing macrophage polarization via CD44, a master immunoregulator in mesenchymal stem cells.
支气管肺发育不良（BPD）是由新生儿和婴儿的高氧引起的，导致肺部损伤和异常的肺功能。然而，目前 BPD 的治疗方法是类固醇和药物治疗，这会导致神经发育障碍。使用脐带血来源的间充质干细胞（UCB-MSCs）治疗是一种有效的替代方法。为了预防 BPD 中的肺部炎症，本研究假设间充质干细胞分泌的一种关键调节因子将炎症性巨噬细胞极化为炎症部位的抗炎巨噬细胞。与间充质干细胞共培养的脂多糖诱导的巨噬细胞分泌低水平的炎性细胞因子 IL-8 和 IL-6，但高水平的抗炎细胞因子 IL-10。沉默间充质干细胞中的核心蛋白聚糖会抑制 CD44 的表达，而 CD44 介导巨噬细胞中的抗炎活性。在高氧肺损伤大鼠模型中检查了间充质干细胞的作用。巨噬细胞的极化取决于间充质干细胞分泌的核心蛋白聚糖的水平。此外，通过下调核心蛋白聚糖，气管内注射沉默核心蛋白聚糖的间充质干细胞或分泌低水平核心蛋白聚糖的间充质干细胞证实了受损肺组织的肺泡化受损。在组织中，通过 CD44 观察到抗炎性巨噬细胞标志物 CD163 的减少。因此，我们确定核心蛋白聚糖是一种关键的旁分泌因子，通过间充质干细胞中的 CD44 诱导巨噬细胞极化，CD44 是间充质干细胞中的主要免疫调节剂。
