间充质干细胞预处理策略在严重烧伤治疗中的潜力

Potential of mesenchymal stem cell preconditioning strategies in the treatment of severe burn injury

背景:间充质干细胞是再生医学中的理想候选者,目前其临床应用受限于由移植微环境改变导致的细胞存活率降低和旁分泌能力差。预处理策略被认为可以最大限度地提高间充质干细胞在移植微环境的存活率和生物学作用,为严重烧伤的治疗提供新思路和潜力。目的:对间充质干细胞预处理策略在严重烧伤治疗中的潜力进行综述。方法:以“间充质干细胞,严重烧伤,间充质干细胞预处理,烧伤病理生理学,严重烧伤”和“mesenchymal stem cells,MSCs,preconditioning,pretreatment,burn injury,severe burn injury,burn pathophysiology”为检索词,在中国知网数据库和PubMed数据库检索自2000年1月至2022年1月收录的论著和综述,并将其进行筛选和分析,排除研究内容不符、陈旧、重复性文献,以及可信度低、逻辑严谨性差的文献,最终选择81篇文献进行综述。结果与结论:①严重烧伤后传统救治方法为液体复苏、气道管理、感染防控、脏器支持、早期焦痂切开减压及切削痂自体和异体皮移植,临床治疗依然面临很大的挑战;②间充质干细胞因其低免疫原性、易获取、组织修复能力强等优点成为治疗的热点;③间充质干细胞一旦被应用于烧伤创面,就会面临缺血缺氧、活性氧产生增加引起的氧化应激环境,导致细胞存活率和生物学活性降低;④细胞因子预处理、低氧预处理、基因修饰和药物预处理等策略可以在严重烧伤病理进展的不同阶段发挥治疗创面感染、减轻过度炎症、缓解高代谢状态、调节免疫系统、促进创面愈合、抑制增生性瘢痕的治疗潜力;⑤由于严重烧伤患者少,没有足够的临床数据支持,限制了预处理策略在严重烧伤临床治疗中的应用;⑥需要通过大量的临床前研究和临床病例确定预处理策略在严重烧伤治疗中的有效性和安全性。

BACKGROUND:Mesenchymal stem cells are ideal candidates in regenerative medicine,and their clinical application is currently limited by reduced cell viability and poor paracrine capacity caused by changes in the transplanted microenvironment.The preconditioning strategy is believed to maximize the survival rate and biological role of mesenchymal stem cells in the transplanted microenvironment,providing new ideas and potential for the treatment of severe burn injuries.OBJECTIVE:To review the potential of mesenchymal stem cell preconditioning strategies in the treatment of severe burn injuries.METHODS:With“mesenchymal stem cells,MSCs,preconditioning,pretreatment,burn injury,severe burn injury,burn pathophysiology”as the search terms in Chinese and English,the original articles and reviews collected from January 2000 to January 2022 in CNKI database and PubMed database were searched,and screened and analyzed.Finally,81 articles were selected for review after excluding researches that were not related to this publication,inconsistent,outdated and repetitive,and those with low credibility and poor logical rigor.RESULTS AND CONCLUSION:(1)The traditional treatment methods after severe burn injury are fluid resuscitation,airway management,infection prevention and control,organ support,early eschar decompression and eschar autograft and allograft transplantation.Clinical treatment still faces great challenges.(2)Mesenchymal stem cells have become a hot spot for treatment because of their low immunogenicity,easy access,and strong tissue repair ability.(3)Once mesenchymal stem cells are applied to burn wounds,they will face the oxidative stress environment caused by ischemia/hypoxia and increased production of reactive oxygen species,resulting in decreased cell survival rate and biological activity.(4)Strategies such as cytokine preconditioning,hypoxia preconditioning,gene modification and drug preconditioning can play a role in treating wound infection,reducing excessive inflammation,relieving hypermetabolic state,regulating immune system,promoting wound healing,and inhibiting therapeutic potential of hypertrophic scars.(5)The application of pretreatment strategies in the clinical treatment of severe burn injuries is limited due to the small number of patients with severe burns and insufficient clinical data to support them.(6)The efficacy and safety of preconditioning strategies in the treatment of severe burn injuries need to be determined through a large number of preclinical studies and clinical cases.