Imaizumi Mitsuyoshi, Li-Jessen Nicole Y K, Sato Yuka, Yang David T, Thibeault Susan L
1 Department of Otolaryngology, School of Medicine, Fukushima Medical University, Fukushima City, Japan.
2 School of Communication Sciences and Disorders, McGill University, Montreal, QC, Canada.
Ann Otol Rhinol Laryngol. 2017 Apr;126(4):304-314. doi: 10.1177/0003489417691296. Epub 2017 Feb 12.
One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds.
Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls. Hyaluronic acid hydrogel scaffold, HA hydrogel scaffold containing hiPS, and HA hydrogel scaffold containing hiPS with epidermal growth factor (EGF) were injected in both vocal folds immediately after surgery. One and 2 weeks after injection, larynges were excised for histology, immunohistochemistry, and fluorescence in situ hybridization (FISH).
Presence of HA hydrogel was confirmed in vocal folds 1 and 2 weeks post injection. The FISH analysis confirmed the presence and viability of hiPS in the injected vocal folds. Histological results demonstrated that vocal folds injected with HA hydrogel scaffold containing EGF demonstrated less fibrosis than those with HA hydrogel only.
Human-iPS survived in injured rat vocal folds. The HA hydrogel with hiPS and EGF ameliorated the fibrotic response. Additional work is necessary to optimize hiPS differentiation and further confirm the safety of hiPS for clinical applications.
一种用于声带瘢痕形成的前瞻性治疗选择是使用含有诱导多能干细胞（iPS）的工程支架进行再生。在本研究中，我们研究了利用包裹人诱导多能干细胞（hiPS）的可注射透明质酸（HA）支架进行声带再生的可行性。
30只无胸腺裸鼠接受单侧声带损伤。对侧声带作为未受伤的对照。术后立即在双侧声带中注射透明质酸水凝胶支架、含有hiPS的HA水凝胶支架以及含有hiPS和表皮生长因子（EGF）的HA水凝胶支架。注射后1周和2周，切除喉部进行组织学、免疫组织化学和荧光原位杂交（FISH）检查。
注射后1周和2周在声带中均证实存在HA水凝胶。FISH分析证实了注射的声带中hiPS的存在和活力。组织学结果表明，注射含有EGF的HA水凝胶支架的声带比仅注射HA水凝胶的声带纤维化程度更低。
人诱导多能干细胞在受伤的大鼠声带中存活。含有hiPS和EGF的HA水凝胶改善了纤维化反应。需要进一步开展工作以优化hiPS的分化并进一步确认hiPS在临床应用中的安全性。
