中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (7): 1133-1140.doi: 10.12307/2023.083

• 生物材料综述 biomaterial review • 上一篇    下一篇

纳米材料多模态显像示踪技术在间充质干细胞治疗尘肺中的应用

薛  婷，张新日，孔晓梅   

  1. 国家卫健委尘肺病重点实验室，呼吸疾病防治与基础研究山西省重点实验室，山西医科大学第一医院呼吸与危重症医学科，山西省太原市  030001
  • 收稿日期:2022-03-03 接受日期:2022-04-18 出版日期:2023-03-08 发布日期:2022-07-20
  • 通讯作者: 孔晓梅，女，主任医师，硕士生导师，国家卫健委尘肺病重点实验室，呼吸疾病防治与基础研究山西省重点实验室，山西医科大学第一医院呼吸与危重症医学科，山西省太原市 030001
  • 作者简介:薛婷，女，1988年生，山西省太原市人，汉族，讲师，主要从事尘肺干细胞治疗研究。
  • 基金资助:
    山西省自然科学基金基础研究计划项目(20210302124039)，项目负责人：薛婷；山西省高等学校科技创新项目(2020L0201)，项目负责人：薛婷；山西医科大学省级博士基金项目(SD1905)，项目负责人：薛婷；山西医科大学校级博士启动基金项目(XD1905)，项目负责人：薛婷

Mesenchymal stem cell therapy for pneumoconiosis using nanomaterials combined with multi-modal molecular imaging

Xue Ting, Zhang Xinri, Kong Xiaomei   

  1. National Health Commission Key Laboratory of Pneumoconiosis, Key Laboratory of Prophylaxis and Treatment and Basic Research for Respiratory Diseases of Shanxi Province, Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Received:2022-03-03 Accepted:2022-04-18 Online:2023-03-08 Published:2022-07-20
  • Contact: Kong Xiaomei, Chief physician, Master’s supervisor, National Health Commission Key Laboratory of Pneumoconiosis, Key Laboratory of Prophylaxis and Treatment and Basic Research for Respiratory Diseases of Shanxi Province, Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • About author:Xue Ting, Lecturer, National Health Commission Key Laboratory of Pneumoconiosis, Key Laboratory of Prophylaxis and Treatment and Basic Research for Respiratory Diseases of Shanxi Province, Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Supported by:
    the Basic Research Project of Natural Science in Shanxi Province, No. 20210302124039 (to XT); the Scientific and Technological Innovation Program of Higher Education Institutions in Shanxi Province, No. 2020L0201 (to XT); the Start-up Foundation for Doctoral Scientific Research of Shanxi Province, No. SD1905 (to XT); the Start-up Foundation for Doctoral Scientific Research of Shanxi Medical University, No. XD1905 (to XT)

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摘要：

文题释义：
多模态分子影像技术：是一种将具有多种显像功能的特异性或非特异性的分子探针同时导入体内，融合不同影像学技术优势，运用多种影像成像检测手段，在体实时、特异及精准地探测体内病变部位复杂的生物过程，可更加全面地提供病变过程中解剖结构、组织学特征、功能代谢、生物化学指标、生理病理及分子细胞等多水平多信息的分子影像技术，其在肿瘤的早期诊断、基因及靶向药物示踪治疗、个性化检测、特定细胞群及功能分子监测、判断预后和评价疗效等方面具有广阔的应用前景。
尘肺病：是劳动者因长期吸入职业活动中不同致病矿物性粉尘，并在肺内蓄积，引起的以不可逆肺组织弥漫性纤维化为主要病理特征的全身性疾病。

背景：临床前研究表明间充质干细胞可用于尘肺病的治疗，然而由于缺乏体内有效的间充质干细胞示踪技术，相关研究尚停滞于临床前探索，因此间充质干细胞示踪技术的发展是解决此问题的关键。
目的：综述尘肺治疗现状、间充质干细胞治疗尘肺以及纳米材料多模态显像示踪技术在间充质干细胞治疗尘肺的研究进展，评价不同类型纳米材料多模态显像示踪技术在间充质干细胞治疗尘肺研究现状中的贡献、效果及前景，分析目前存在的问题及其未来的发展方向。
方法：以PubMed为检索数据库，以“pneumoconiosis，pulmonary fibrosis，stem cells，MSCs，trace，nanoparticles，multi-modal imaging，therapy”为关键词进行检索，检索文献时限为2016-2021年，依据纳入和排除标准，最终纳入符合要求的60篇文献进行综述。
结果与结论：①目前的临床前研究显示，金纳米颗粒、磁靶向纳米颗粒及近红外长余辉发光纳米颗粒3种材料设计精巧且新颖，具有良好的生物相容性、稳定性、安全性和多模态成像能力等优点，在间充质干细胞治疗尘肺过程中体内示踪及发挥抗肺纤维化作用疗效评价的临床前应用初显成效，示踪长效性、靶向定位、余辉光学性能顺次分别是上述3种纳米材料的优势。②金纳米颗粒是纳米材料联合多模态显像示踪技术在间充质干细胞治疗尘肺的临床应用中最具应用前景的纳米材料，很大程度上推动了间充质干细胞治疗尘肺领域的进展与临床转化。③纳米材料多模态显像示踪的研究为实现间充质干细胞治疗尘肺的临床应用提供了可靠的新技术，对进一步推进靶向治疗尘肺的临床转化应用与实践具有重要的意义。④在精准医疗引领的新时代，阐明间充质干细胞治疗尘肺机制，解决增强纳米材料标记间充质干细胞的靶向积累、提高间充质干细胞摄取和控制缓释效力、延长药物半衰期以及维持稳定血药浓度等关键问题，以及如何将高度整合的纳米材料多模态成像与具有多重治疗功能且可生物降解和体内清除的诊疗一体化载药体系相结合，尚需未来更为深入及详尽的探索。

http://orcid.org/0000-0002-1009-0674(薛婷)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 尘肺, 肺纤维化, 干细胞, 间充质干细胞, 示踪, 纳米材料, 多模态显像, 治疗

Abstract: BACKGROUND: Previous studies indicate that mesenchymal stem cells are used for therapy of pneumoconiosis. However, related studies are still at the stage of preclinical research due to a lack of effective tracing techniques in vivo for mesenchymal stem cells. Therefore, these effective tracing techniques in vivo for stem cells are the key to solve it. 
OBJECTIVE: To review the research progresses of present therapy situations for pneumoconiosis, related studies on mesenchymal stem cell therapy for pneumoconiosis and different nanoparticles combined with multi-modal molecular imaging in mesenchymal stem cell therapy for pneumoconiosis, evaluate the contribution, effect and prospect of different types of nanomaterials multi-modal imaging tracking technology in the research status of mesenchymal stem cell therapy for pneumoconiosis, and analyze the present problems and future development directions. 
METHODS: PubMed database was searched for articles published from 2016 to 2021. Key words were “pneumoconiosis, pulmonary fibrosis, stem cells, MSCs, trace, nanoparticles, multi-modal imaging, therapy”. According to the inclusion and exclusion criteria, 60 relevant articles were finally included for review. 
RESULTS AND CONCLUSION: (1) Preclinical studies indicate that gold nanoparticles, magnetic nanoparticles and near-infrared-long persistent luminescence nanoparticles are innovative and ingenious in design with a series of advantages such as biocompatibility, stability, safety and capabilities of multi-modal imaging. Initial effectiveness is achieved in preclinical applications of in vivo tracking and anti-fibrosis therapeutic evaluation in the process of anti-pulmonary fibrosis treatment of mesenchymal stem cells. Meanwhile, each nanoparticle has its own advantages, for instance, long-term in vivo tracking, targeting special localization and long persistent luminescence respectively are merits of the gold nanoparticles, magnetic nanoparticles and near-infrared-long persistent luminescence nanoparticles. (2) Gold nanoparticles are the most promising nanoparticles of clinical application in the studies on the mesenchymal stem cell therapy for pneumoconiosis using nanoparticles combined with multi-modal molecular imaging, to a large extent, which promote the progress and clinical transformation in the area of mesenchymal stem cell therapy for pneumoconiosis. (3) Reliable technology of research on nanoparticles combined with multi-modal molecular imaging is provided to clinical application for realizing the mesenchymal stem cell therapy for pneumoconiosis. It is of great significance for propelling the clinical transformation and application of technology of targeting therapy for pneumoconiosis. (4) In the era of precision medicine, further study and detailed exploration are needed in the future to elucidate the mechanism of mesenchymal stem cell therapy for pneumoconiosis, to solve the critical problems including enhancing the targeted accumulation of nanoparticles-labeled mesenchymal stem cells, increasing the cellular uptake, controlling sustained release efficacy, prolonging the half-life of drugs and maintaining stable blood concentration, and how to combine multi-modal molecular imaging of nanoparticles with the diagnosis-and-treatment integration of drug delivery system with versatile therapeutic functions and biodegradable and cleared in vivo characteristics. 

Key words: pneumoconiosis, pulmonary fibrosis, stem cell, mesenchymal stem cell, trace, nanomaterial, multi-modal imaging, therapy

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