Introduction

Endoscopic sinus surgery is an effective surgical procedure for treating chronic sinusitis; however, extensive exposure of the bone in the nasal cavity can result in permanent disability postoperatively. Particularly, closure of the sinus drainage pathway due to bone hyperplasia associated with bone exposure can trigger the recurrence of sinusitis. It is essential to regenerate the nasal mucosa after surgery to avoid bone hyperplasia. Regenerative medicine, including cell therapy, could be one of the leading options for nasal mucosa regeneration. To date, there is a lack of effective models for evaluating treatments for prevention of bone hyperplasia that occurs after sinus surgery. The purpose of this study was to develop a model of nasal mucosal removal to evaluate cellular therapies.

Methods

The model was created in rabbits, a species with a wide nasal structure, and was generated by approaching the maxillary sinus from the nasal bone side and solely removing the maxillary sinus mucosa without destroying the structures in the nasal cavity. Adipose-derived mesenchymal stromal cell sheets prepared in temperature-responsive cell culture dishes were examined for the effect of transplantation in the animal model. Intranasal evaluation was assessed by micro-computed tomography and tissue staining.

Results

Significant bone hyperplasia in the maxillary sinus occurred on the side of mucosal removal, and no bone hyperplasia occurred in the control sham side in the same rabbits on postoperative day 28. Bone hyperplasia was observed over a short time period, with the presence of bone hyperplasia in the maxillary sinus on day 14 and calcification of the bone on day 28. The adipose-derived mesenchymal stromal cell (ADSC) sheet was transplantable in a nasal mucosa-removal model. No significant differences in bone hyperplasia were found between the transplantation side and the sham side in terms of the effect of transplantation of the ADSC sheet; however, bone hyperplasia tended to be suppressed on the transplantation side.

Conclusions

This animal model is simple, highly reproducible, and does not require special equipment or drugs. In addition, this model can be used for various therapeutic interventions, including cell therapy. The presence or absence of the nasal mucosa affects bone remodeling, which highlights the importance of regeneration of the nasal mucosa. In the nasal mucosal regeneration therapy, the ADSC sheet had an inhibitory effect on bone hyperplasia. The nasal mucosa-removal model allows observation of conditions associated with nasal mucosa removal and evaluation of the effectiveness of cell therapy.

中文翻译：

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开发用于评估细胞疗法的鼻粘膜去除模型

介绍

内窥镜鼻窦手术是治疗慢性鼻窦炎的有效手术方式；然而，鼻腔中的骨骼大量暴露会导致术后永久性残疾。特别是，由于与骨暴露相关的骨增生导致鼻窦引流通路的关闭会引发鼻窦炎的复发。手术后必须再生鼻粘膜以避免骨质增生。包括细胞疗法在内的再生医学可能是鼻粘膜再生的主要选择之一。迄今为止，缺乏有效的模型来评估预防鼻窦手术后发生的骨增生的治疗方法。本研究的目的是开发一种鼻粘膜切除模型来评估细胞疗法。

方法

该模型是在具有宽鼻结构的兔子中创建的，它是通过从鼻骨侧接近上颌窦并仅去除上颌窦粘膜而不破坏鼻腔中的结构而生成的。在动物模型中检查了在温度响应性细胞培养皿中制备的脂肪来源的间充质基质细胞片的移植效果。通过微型计算机断层扫描和组织染色评估鼻内评估。

结果

切除黏膜侧上颌窦明显骨质增生，术后第28天同兔对照组假侧未见骨质增生。在短时间内观察到骨质增生，有骨质增生第 14 天在上颌窦中，第 28 天骨骼钙化。脂肪来源的间充质基质细胞 (ADSC) 片可移植到鼻粘膜切除模型中。在ADSC片的移植效果方面，移植侧和假手术侧的骨质增生没有显着差异；然而，骨增生倾向于在移植侧受到抑制。

结论

这种动物模型简单、可重复性高，不需要特殊设备或药物。此外，该模型可用于各种治疗干预，包括细胞治疗。鼻黏膜的存在与否影响骨骼重塑，这凸显了鼻黏膜再生的重要性。在鼻黏膜再生治疗中，ADSC片材对骨质增生有抑制作用。鼻粘膜切除模型允许观察与鼻粘膜切除相关的情况并评估细胞疗法的有效性。