中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (15): 2427-2434.doi: 10.12307/2023.607

• 干细胞综述 stem cell review • 上一篇    下一篇

经血来源干细胞及其外泌体的应用现状和前景

马羽就1,2,张旭东1,2,谭季春1,2   

  1. 1中国医科大学附属盛京医院生殖医学中心,辽宁省沈阳市   110022;2辽宁省生殖障碍疾病与生育力重塑重点实验室,辽宁省沈阳市   110022
  • 收稿日期:2022-06-15 接受日期:2022-07-21 出版日期:2023-05-28 发布日期:2022-10-18
  • 通讯作者: 谭季春,博士,博士生导师,中国医科大学附属盛京医院生殖中心生殖二科,辽宁省沈阳市 110022;辽宁省生殖障碍疾病与生育力重塑重点实验室,辽宁省沈阳市 110022
  • 作者简介:马羽就,女,1999年生,辽宁省人,汉族,中国医科大学附属盛京医院在读硕士,主要从事生殖医学方面的研究。
  • 基金资助:
    国家自然科学基金面上项目(82071601),项目负责人:谭季春;辽宁省中央引导地方科技发展专项项目(2020JH6/10500006),项目负责人:谭季春;辽宁省重点研发计划项目(2018225093),项目负责人:谭季春;中国医科大学学科提升计划,项目负责人:谭季春;盛京自由研究者基金,项目负责人:谭季春

Application status and prospect of menstrual blood-derived stem cells and their exosomes

Ma Yujiu1, 2, Zhang Xudong1, 2, Tan Jichun1, 2   

  1. 1Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China; 2Key Laboratory for Reproductive Disorder and Fertility Remodeling of Liaoning Province, Shenyang 110022, Liaoning Province, China
  • Received:2022-06-15 Accepted:2022-07-21 Online:2023-05-28 Published:2022-10-18
  • Contact: Tan Jichun, MD, Doctoral supervisor, Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China; Key Laboratory for Reproductive Disorder and Fertility Remodeling of Liaoning Province, Shenyang 110022, Liaoning Province, China
  • About author:Ma Yujiu, Master candidate, Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China; Key Laboratory for Reproductive Disorder and Fertility Remodeling of Liaoning Province, Shenyang 110022, Liaoning Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82071601 (to TJC); the Liaoning Province Central Leading Local Science and Technology Development Special Project, No. 2020JH6/10500006 (to TJC); the Liaoning Province Key Research and Development Program Project, No. 2018225093 (to TJC); Subject Enhancement Program of China Medical University (to TJC); the Shengjing Free Investigator Fund (to TJC)

摘要:

文题释义:
经血来源干细胞:是从女性月经血中提取的,具有多向分化潜能的间充质干细胞。其具有很强的增殖能力,在体外倍增时间为数小时,在多次传代下仍能保证细胞核型和染色体稳定,有定向趋化能力,也可分化为多种功能性细胞,可调节免疫反应并以旁分泌途径分泌各种生物活性成分,促进组织和细胞再生。
经血来源干细胞外泌体:是经血来源干细胞发挥旁分泌功能的主要物质,属于胞外囊泡的一种,粒径大小为30-150 nm,其中含有脂质、RNA和蛋白质,从间充质干细胞中提取的外泌体在组织再生和损伤恢复方面具有与其来源细胞相同的功效。

背景:经血来源干细胞是从女性月经血中提取的,有多向分化潜能的间充质干细胞,具有易获取、弱免疫原性、增殖能力强、传代稳定及无伦理争议等特点。经血来源干细胞中提取的外泌体在组织再生和损伤恢复方面具有与经血来源干细胞相同的功效。经血来源干细胞及其外泌体已经在多种疾病治疗的临床前研究和临床研究中取得了令人兴奋的成果。
目的:文章将就经血来源干细胞及其外泌体相关的基础研究与临床应用研究进展及未来潜在的应用前景和需要考虑的问题加以综述。
方法:应用计算机检索PubMed、中国知网期刊全文数据库2000-2022年与经血来源干细胞和经血来源干细胞外泌体相关的文献,最终筛选出75篇进行综述分析。
结果与结论:①经血来源干细胞是具有多向分化功能的间充质干细胞,具有来源丰富、免疫原性弱和增殖能力强的特点。②经血来源干细胞外泌体是发挥经血来源干细胞旁分泌功能的主要介质,在促进组织再生和损伤修复方面具有与来源细胞相同的功效。二者都具有抗炎、抗凋亡和促进组织器官功能恢复的能力,并在各系统疾病的动物实验模型中展现了较为优秀的治疗水平,其中经血来源干细胞已经在宫腔粘连、充血性心力衰竭、多发性硬化及病毒性肺炎等疾病中应用于临床患者,在没有产生肿瘤或过敏反应等不良作用的情况下显著延缓了疾病的进展。③但从经血来源干细胞从2007年被发现至今只过了短短15年,因此经血来源干细胞及其外泌体具有试验样本不足和应用年限过短的短板,仍需长期的临床前研究验证其安全性和有效性,此外,要真正应用于临床,也需要找到更加规范的给药方式,因此未来出台相关应用指南也是必要的。④经血来源干细胞及其外泌体结合三维支架技术已在盆腔器官脱垂、糖尿病导致的皮肤损伤、骨软骨缺损及膀胱壁重建的动物实验研究中验证了治疗的有效性,未来希望借助经血来源干细胞及其外泌体的各种优点与组织工程学和材料学相结合,逐步开展临床研究。
https://orcid.org/0000-0002-7217-4611 (马羽就);https://orcid.org/0000-0002-6401-1919 (谭季春) 
中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: 经血源性间充质干细胞, 干细胞, 外泌体, 旁分泌, 干细胞治疗, 免疫调节, 组织修复, 细胞凋亡

Abstract: BACKGROUND: Menstrual blood-derived stem cells are derived from female menstrual blood. Mesenchymal stem cells with multidirectional differentiation potential are easily accessible, weakly immunogenic, highly proliferative, stable passage, and free from ethical controversy. Exosomes derived from menstrual blood-derived stem cells have the same efficacy as menstrual blood-derived stem cells in tissue regeneration and injury recovery. Menstrual blood-derived stem cells and their exosomes have yielded exciting results in preclinical and clinical studies for the treatment of various diseases.  
OBJECTIVE: To review the progress of basic research and clinical applications related to menstrual blood-derived stem cells and their exosomes, as well as the potential future applications and issues to be considered.
METHODS: A computerized search of PubMed and the CNKI database from 2000 to 2022 for literature related to menstrual blood-derived stem cells and menstrual blood-derived stem cell exosomes was conducted. Finally, 75 articles were selected for review analysis.  
RESULTS AND CONCLUSION: (1) Menstrual blood-derived stem cells are mesenchymal stem cells with multidirectional differentiation function, characterized by abundant source, weak immunogenicity and high proliferative capacity. (2) The exosomes are the main mediators of the paracrine function of menstrual blood-derived stem cells and have the same efficacy as the source cells in promoting tissue regeneration and injury repair. Both have the ability to be anti-inflammatory, anti-apoptotic and promote tissue and organ function recovery, and have demonstrated more excellent therapeutic levels in animal test models of various systemic diseases, where menstrual blood-derived stem cells have been used in clinical patients in diseases such as uterine adhesions, congestive heart failure, multiple sclerosis and viral pneumonia, and have greatly delayed the disease progression without producing side effects such as tumor or allergic reactions. (3) However, only 15 years have passed since the discovery of menstrual blood-derived stem cells in 2007. Therefore, menstrual blood-derived stem cells and their exosomes have the shortcomings of insufficient samples and short years of application. Long-term preclinical trials are still needed to verify their safety and efficacy. In addition, to be truly applied in clinical practice, it is also necessary to find a more standardized way of administration, so it is necessary to issue relevant application guidelines in the future. (4) The combination of menstrual blood-derived stem cells and their exosomes with 3D scaffold technology has been used in animal trials for pelvic organ prolapse, skin damage due to diabetes, osteochondral defects, and bladder wall reconstruction. More clinical applications can be developed in the future by combining various advantages of menstrual blood-derived stem cells and their exosomes with tissue engineering and material science to gradually carry out clinical research.

Key words: menstrual blood-derived mesenchymal stem cell, stem cell, exosome, paracrine, stem cell therapy, immunomodulation, tissue repair, apoptosis

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