Mesenchymal treatment of the salivary glands upregulates proteins with regenerative potential in irradiated patients

Damage to the major salivary glands is the leading long-term side effect to radiation therapy in patients with head and neck cancerof radiation of head and neck cancers,. It resultresultsing in severe hyposalivationdry mouth , which profoundly impairs basic physiological functions for patients such as speaking, eating, tasting, and swallowing. TodayCurrently, no effective treatment can be offeredexists to alleviate radiation-induced hyposalivation, but recently, treatment with adipose tissue-derived mesenchymal stem/stromal cells (ASC) hasve very recently been tested as a newshowed potential treatment modalityfor restoring the function of the salivary glands. However, the impact of ASC-treatments on the salivary gland proteinome composition has notever been testedinvestigated. HereIn this study, we examine the salivary gland proteomeuse in patients with severe hyposalivation due to radiation therapy and in healthy controls using quantitative metaproteomics. Furthermore, to 1: compare the salivary proteome in patients with severe hyposalivation to that of healthy controls, and 2: towe addresslongitudinally monitorinvestigate the effect of ASC ASC-treatment on the salivary gland proteome. We identify that treatment with ASC-treatments results inis associated with the upregulation of specific proteins in saliva 120 days after injection. Therefore, oOur data findings suggest that ASCs to stimulate biological processes in the salivary gland tissue, which could have beneficial clinical effects.

头颈部癌症患者接受放射治疗后，主要唾液腺损伤是其最常见的长期放疗不良反应。该损伤会引发严重的唾液分泌减少（口干症），严重损害患者的言语、进食、味觉感知及吞咽等基本生理功能。目前尚无有效疗法可缓解放疗诱导的唾液分泌减少，但近期有研究将脂肪组织来源间充质干/基质细胞（adipose tissue-derived mesenchymal stem/stromal cells, ASC）作为修复唾液腺功能的潜在治疗手段进行了探索。然而，目前尚未有研究探讨ASC疗法对唾液腺蛋白质组组成的影响。本研究采用定量宏蛋白质组学技术，对放疗后出现严重唾液分泌减少的患者及健康对照者的唾液蛋白质组进行分析。本研究的研究目标包括两点：其一，对比严重唾液分泌减少患者与健康对照者的唾液蛋白质组差异；其二，纵向探究ASC疗法对唾液腺蛋白质组的影响。研究发现，在细胞注射后120天，ASC疗法与唾液中特定蛋白质的表达上调存在关联。因此，本研究结果表明，ASC可激活唾液腺组织内的生物学过程，有望产生有益的临床疗效。