Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
Department of Dental Medicine, Karolinska Institute, Stockholm, Sweden.
Laryngoscope. 2020 Jan;130(1):E21-E29. doi: 10.1002/lary.27885. Epub 2019 Mar 5.
OBJECTIVES/HYPOTHESIS: This study aimed to determine whether local injection of human mesenchymal stromal cells (MSC) could modulate the early inflammatory response within injured vocal folds (VFs) to promote wound-healing processes.
Experimental xenograft model.
VF injury was surgically induced by bilateral resection of the lamina propria of rabbits, and MSC were immediately injected into the injured area of both VFs. Animals were sacrificed on days 2, 4, and 24. Histological analyses were performed by hematoxylin and eosin, Masson's Trichrome, and elastin staining. Cell death was visualized by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and the M2 macrophage marker, CD163, detected by immunohistochemistry. Persistence of injected MSC was evaluated by fluorescent in situ hybridization (FISH). Quantitative polymerase chain reaction was performed on the contralateral VF.
Histological examination at days 2 and 4 indicated that MSC were able to reduce tissue inflammation, with gene expression analysis confirming a significant reduction of proinflammatory markers, interleukin (IL)-1β, and IL-8. FISH demonstrated low-level persistence of injected MSC at both time points, and TUNEL confirmed localized cell death at the injury site. Increased levels of CD163+ anti-inflammatory macrophages indicated a change in the immune milieu, supporting wound resolution. Evidence of a more organized collagen matrix suggests that MSC may enhance the production of a functional repair tissue after injury, despite their low-level persistence within the tissue.
This study demonstrates that MSC are able to positively modulate the early wound-healing response through resolution of the inflammatory phase and promotion of tissue repair.
NA Laryngoscope, 130:E21-E29, 2020.
目的/假设：本研究旨在确定人间质基质细胞（MSC）的局部注射是否可以调节受伤声带（VF）内的早期炎症反应，以促进伤口愈合过程。
实验性异种移植物模型。
通过双侧切除兔的固有层来诱导 VF 损伤，并立即将 MSC 注射到双侧 VF 的损伤区域。动物在第 2、4 和 24 天被处死。通过苏木精和伊红、马松三色和弹性蛋白染色进行组织学分析。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）可视化细胞死亡，并通过免疫组织化学检测 M2 巨噬细胞标志物 CD163。通过荧光原位杂交（FISH）评估注射 MSC 的持久性。对对侧 VF 进行定量聚合酶链反应。
第 2 和 4 天的组织学检查表明，MSC 能够减少组织炎症，基因表达分析证实促炎标志物白细胞介素（IL）-1β和 IL-8 显著减少。FISH 显示在两个时间点都有低水平的注射 MSC 持续存在，TUNEL 证实损伤部位存在局部细胞死亡。增加的 CD163+抗炎巨噬细胞表明免疫环境发生了变化，支持伤口愈合。有组织的胶原基质的证据表明，尽管 MSC 在组织内的持续时间较低，但它们可能在受伤后增强功能性修复组织的产生。
本研究表明，MSC 能够通过炎症阶段的解决和组织修复来积极调节早期伤口愈合反应。
无。喉科，130：E21-E29，2020。
