Nicolas Larissa, Mandl Hanna, Schrader Feng, Long Jennifer L
David Geffen School of Medicine at University of California-Los Angeles Los Angeles California USA.
Research Service Greater Los Angeles VAHS Los Angeles California USA.
Laryngoscope Investig Otolaryngol. 2024 Oct 9;9(5):e70007. doi: 10.1002/lio2.70007. eCollection 2024 Oct.
Cell-based outer vocal fold replacement (COVR) offers a potential treatment for severe vocal fold scarring or cancer reconstruction. Previous work in rabbits using human adipose-derived stem cells (ASC) in fibrin suggested that a hybrid structure emerged within 2 months, containing both implanted and host cells. This project uses immunocytochemistry to better define the phenotypic fate of implanted cells and features of the extracellular environment.
Immunocytochemistry was performed on sections collected from rabbits 2 months after COVR implantation or scar surgery. Cellular targets included human leukocyte antigen (HLA), CD31, and smooth muscle actin (SMA).
HLA was present in all implanted sections and was used to identify human cells. In adjacent sections, HLA-positive cells were identified expressing CD31. SMA was not identified in the same cells as HLA. These markers were also present in injured vocal folds not receiving COVR. SMA protein content did not differ according to treatment.
Implanted human ASC persist in rabbit vocal folds. Some appear to express CD31, an endothelial marker. Smooth muscle actin, a marker of myofibroblast phenotype, was present in all sections regardless of treatment, and was not identified in hASC. Host cells also infiltrate the structure, producing a hybrid host-graft vocal fold.
基于细胞的声带外侧替代术(COVR)为严重声带瘢痕或癌症重建提供了一种潜在的治疗方法。先前在兔子身上使用人脂肪干细胞(ASC)与纤维蛋白的研究表明,在2个月内会出现一种混合结构,其中包含植入细胞和宿主细胞。本项目使用免疫细胞化学来更好地确定植入细胞的表型命运以及细胞外环境的特征。
对COVR植入或瘢痕手术后2个月的兔子所取切片进行免疫细胞化学检测。细胞靶点包括人类白细胞抗原(HLA)、CD31和平滑肌肌动蛋白(SMA)。
所有植入切片中均存在HLA,用于识别人类细胞。在相邻切片中,发现HLA阳性细胞表达CD31。未在与HLA相同的细胞中鉴定出SMA。这些标志物在未接受COVR的受损声带中也存在。SMA蛋白含量根据治疗情况无差异。
植入的人ASC在兔子声带中持续存在。一些似乎表达CD31,一种内皮标志物。无论治疗情况如何,所有切片中均存在平滑肌肌动蛋白,一种肌成纤维细胞表型的标志物,且在人ASC中未鉴定出。宿主细胞也浸润该结构,形成宿主 - 移植物混合声带。