放射性唾液腺功能损伤的再生医学研究——从干细胞到无细胞治疗

Regenerative medicine research on radiation?-induced salivary gland dysfunction:From stem cell therapy to cell?-free therapy

头颈部肿瘤患者行放射治疗导致的唾液腺组织放射性功能损伤,是常见的并发症,并对患者造成终身影响。干细胞治疗在修复放射性唾液腺功能损伤的研究中取得了一定的效果,该方法能使患者口干症得到部分缓解。目前干细胞治疗的研究大多使用的是免疫原性较低的同种异体间充质干细胞(mesenchymal stem cells,MSCs)。然而,干细胞治疗也存在如干细胞来源不足、干细胞与靶器官融合并能否在体内长期存活、分化成功能细胞等问题。研究表明,MSCs在体内主要是通过细胞外囊泡(extracellular vesicles,EVs)或外泌体来调节宿主细胞(包括放射损伤组织中休眠的干细胞)的,以减轻炎症反应等达到组织再生的目的。因此,EVs或外泌体对放射性组织损伤进行无细胞治疗的概念逐渐引起了人们的关注。无细胞治疗不受外泌体剂量的限制,还具有安全、到达组织器官容易等优点,但也存在一些需要进一步研究的问题,比如MSCs外泌体的内容物并非恒定等。本文综述了干细胞治疗、无细胞治疗研究的相关文献,并对这些治疗的研究进行了展望。

Radiation damage to salivary gland tissue caused by radiation therapy in patients with head and neck tumors is a common complication and has a life-long impact on patients.The researches of stem cell therapy in the treatment of these damage have showed that it could partly alleviate the symptoms of xerostomia.Now,the majority of trials focus on low-immunogenicity mesenchymal stem cells(MSCs)for allogeneic administration.However,potential shortcomings of stem cell therapy include the source of stem cells,the fusion of stem cells with target organs and long-term survival in the body,differentiation into functional cells and etc.Most researches have showed that MSCs regulate host cells,including dormant cells of radiation-damaged tissues,and ameliorate inflammation for tissue regeneration via extracellular vesicles(EVs)or exosomes.Therefore,the concept of cell-free therapy on radiation-damaged tissues by EVs or exosomes,is gradually attracting attention.Cell-free therapy is not limited by the dose of exosomes,and has the advantages of safety,easy access to tissues and organs and etc.However,the development of cell-free therapy exhibits its own set of challenges such as the contents of MSC exosomes are not constant.This paper reviews the relevant literature on stem cell therapy and cell-free therapy research,and gives an outlook on the research of these therapies.