Xerostomia or dry mouth are commonly diagnosed in head and neck cancer patients due to salivary gland (SG) epithelial injury after radiotherapy. Regenerative medicine has fetched the opportunity to replace or regenerate the SG epithelia and restore its secretory function. Early adult stem cell transplantation strategies in rodents have recently shown to improve clinical outcomes in radiotherapy-induced xerostomia in Phase 1/2 human trials. Mesenchymal stem cells from adipose tissue are the most promising, although the ones from the labial mucosa, bone marrow, or dental pulp have an attractive therapeutic value after successful findings in ex vivo and in vivo mouse models of SG injury. Emerging approaches using cell-free therapy with cell “extracts”, “soups” or secretome components also exhibit favorable outcomes in the same rodent models. When compared to cell-based approaches, extracellular vesicles (EV) from the secretome (i.e., exosomes) can be easily extracted, quantified, and are more stable for long-term storage and use in SG tissue engineering. Additive manufacturing and three-dimensional bioprinting or bioassembly have an important role on generating spheroids or organoids for cell transplantation to ameliorate SG injury. Moreover, organoids can secrete EV, which may have a therapeutic potential worth to explore in future studies. In this review, we will describe the technological advancements and challenges of these different cell-based and cell-free strategies in SG tissue engineering and regeneration.

中文翻译：

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唾液腺组织工程的趋势：从干细胞到分泌组和类器官生物打印

由于放射治疗后唾液腺 (SG) 上皮损伤，头颈部癌症患者通常会诊断出口干或口干。再生医学抓住了替代或再生SG上皮细胞并恢复其分泌功能的机会。在 1/2 期人体试验中，啮齿类动物的早期成体干细胞移植策略最近显示可改善放疗引起的口干症的临床结果。来自脂肪组织的间充质干细胞是最有前途的，尽管来自唇部粘膜、骨髓或牙髓的间充质干细胞在体外和体内的成功发现后具有有吸引力的治疗价值SG 损伤的小鼠模型。使用细胞“提取物”、“汤”或分泌组成分的无细胞疗法的新兴方法在相同的啮齿动物模型中也表现出良好的结果。与基于细胞的方法相比，来自分泌组（即外泌体）的细胞外囊泡 (EV) 可以轻松提取、量化，并且在长期储存和用于 SG 组织工程时更稳定。增材制造和三维生物打印或生物组装在生成用于细胞移植的球体或类器官以改善 SG 损伤方面具有重要作用。此外，类器官可以分泌 EV，这在未来的研究中可能具有值得探索的治疗潜力。在这次审查中，