Kasai Yoshiyuki, Morino Tsunetaro, Nakayama Tsuguhisa, Yamamoto Kazuhisa, Kojima Hiromi
Department of Otorhinolaryngology The Jikei University School of Medicine Tokyo Japan.
Department of Otorhinolaryngology, Head and Neck Surgery Dokkyo Medical University Tochigi Japan.
FASEB Bioadv. 2022 Dec 19;5(3):89-100. doi: 10.1096/fba.2022-00106. eCollection 2023 Mar.
Understanding the expected efficacy and safety of a new regenerative therapy requires analysis of the fate of the transplanted cell graft. We have shown that transplantation of autologous cultured nasal epithelial cell sheets onto the middle ear mucosa can improve middle ear aeration and hearing. However, it remains unknown whether cultured nasal epithelial cell sheets have the potential to gain mucociliary function in the environment of the middle ear because sampling cell sheets after transplantation is challenging. The present study re-cultured cultured nasal epithelial cell sheets in different culture media and evaluated whether the sheets have the potential to differentiate into airway epithelium. Before re-cultivation, cultured nasal epithelial cell sheets fabricated in keratinocyte culture medium (KCM) contained no FOXJ1-positive and acetyl-α-tubulin-positive multiciliated cells or MUC5AC-positive mucus cells. Interestingly, multiciliated cells and mucus cells were observed when the cultured nasal epithelial cell sheets were re-cultured in conditions that promote differentiation of airway epithelium. However, multiciliated cells, mucus cells and CK1-positive keratinized cells were not observed when cultured nasal epithelial cell sheets were re-cultured in conditions that promote epithelial keratinization. These findings support the suggestion that cultured nasal epithelial cell sheets have the ability to differentiate and gain mucociliary function in response to an appropriate environment (possibly including the environment found in the middle ear) but are unable to develop into an epithelial type that differs from its origins.
要了解一种新的再生疗法的预期疗效和安全性，需要分析移植细胞移植物的命运。我们已经表明，将自体培养的鼻上皮细胞片移植到中耳黏膜上可以改善中耳通气和听力。然而，由于移植后对细胞片进行采样具有挑战性，目前尚不清楚培养的鼻上皮细胞片在中耳环境中是否有获得黏液纤毛功能的潜力。本研究在不同培养基中对培养的鼻上皮细胞片进行再培养，并评估这些细胞片是否有分化为气道上皮的潜力。在再培养之前，在角质形成细胞培养基（KCM）中制备的培养鼻上皮细胞片中不含有FOXJ1阳性和乙酰化α微管蛋白阳性的多纤毛细胞或MUC5AC阳性的黏液细胞。有趣的是，当培养的鼻上皮细胞片在促进气道上皮分化的条件下进行再培养时，观察到了多纤毛细胞和黏液细胞。然而，当培养的鼻上皮细胞片在促进上皮角质化的条件下进行再培养时，未观察到多纤毛细胞、黏液细胞和CK1阳性的角质化细胞。这些发现支持了这样的观点，即培养的鼻上皮细胞片有能力在适当的环境（可能包括中耳环境）中分化并获得黏液纤毛功能，但无法发育成与其起源不同的上皮类型。
