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Guo Zhao, Master candidate, First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250000, Shandong Province, China

郭昭，女，1999年生，山东省招远市人，汉族，山东中医药大学在读硕士，主要从事肛肠疾病临床与基础研究。

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Guo Zhao, Master candidate, First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250000, Shandong Province, China

郭昭，女，1999年生，山东省招远市人，汉族，山东中医药大学在读硕士，主要从事肛肠疾病临床与基础研究。

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Cancer Res. 2016; 76(19): 5832-5844., articleTitle=Mesenchymal Stem Cell-Derived Exosomes Stimulate Cycling Quiescence and Early Breast Cancer Dormancy in Bone Marrow, refAbstract=null), Reference(id=1246459884435296972, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, doi=null, pmid=null, pmcid=null, year=2020, volume=46, issue=2, pageStart=609, pageEnd=620, url=null, language=null, rfNumber=[92], rfOrder=91, authorNames=QIU L, WANG J, CHEN M, journalName=Int J Mol Med, refType=null, unstructuredReference=QIU L, WANG J, CHEN M, et al. Exosomal microRNA-146a derived from mesenchymal stem cells increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2-mediated PI3K/Akt axis. Int J Mol Med. 2020; 46(2): 609-620., articleTitle=Exosomal microRNA-146a derived from mesenchymal stem cells increases the sensitivity of ovarian cancer cells to docetaxel and taxane via a LAMC2-mediated PI3K/Akt axis, refAbstract=null), Reference(id=1246459884506600142, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, doi=null, pmid=null, pmcid=null, year=2021, volume=18, issue=10, pageStart=1408, pageEnd=1423, url=null, language=null, rfNumber=[93], rfOrder=92, authorNames=XU Y, LAI Y, CAO L, journalName=RNA Biol, refType=null, unstructuredReference=XU Y, LAI Y, CAO L, et al. Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-451a represses epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting ADAM10. RNA Biol. 2021; 18(10): 1408-1423., articleTitle=Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-451a represses epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting ADAM10, refAbstract=null), Reference(id=1246459884598874831, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, doi=null, pmid=null, pmcid=null, year=2020, volume=19, issue=null, pageStart=283, pageEnd=293, url=null, language=null, rfNumber=[94], rfOrder=93, authorNames=LUO T, LIU Q, TAN A, journalName=Mol Ther Oncolytics, refType=null, unstructuredReference=LUO T, LIU Q, TAN A, et al. Mesenchymal Stem Cell-Secreted Exosome Promotes Chemoresistance in Breast Cancer via Enhancing miR-21-5p-Mediated S100A6 Expression. Mol Ther Oncolytics. 2020; 19:283-293., articleTitle=Mesenchymal Stem Cell-Secreted Exosome Promotes Chemoresistance in Breast Cancer via Enhancing miR-21-5p-Mediated S100A6 Expression, refAbstract=null), Reference(id=1246459884678566607, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, doi=null, pmid=null, pmcid=null, year=2015, volume=14, issue=15, pageStart=2473, pageEnd=2483, url=null, language=null, rfNumber=[95], rfOrder=94, authorNames=JI R, ZHANG B, ZHANG X, journalName=Cell Cycle, refType=null, unstructuredReference=JI R, ZHANG B, ZHANG X, et al. Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer. Cell Cycle. 2015; 14(15): 2473-2483., articleTitle=Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer, refAbstract=null), Reference(id=1246459884749869777, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, doi=null, pmid=null, pmcid=null, year=2022, volume=13, issue=1, pageStart=138, pageEnd=null, url=null, language=null, rfNumber=[96], rfOrder=95, authorNames=GUO G, TAN Z, LIU Y, journalName=Stem Cell Res Ther, refType=null, unstructuredReference=GUO G, TAN Z, LIU Y, et al. The therapeutic potential of stem cell-derived exosomes in the ulcerative colitis and colorectal cancer. 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优势方面	不同来源间充质干细胞衍生的外泌体	结果
产量	人羊水来源与人骨髓来源相比	人羊水来源间充质干细胞衍生的外泌体产量更高
	犬骨髓来源与犬脂肪来源相比	犬骨髓来源间充质干细胞衍生的外泌体产量更高
组织修复能力	人脐带来源与人骨髓来源、人脂肪来源相比	人脐带来源间充质干细胞衍生的外泌体在组织修复能力上占有优势
免疫调节活性	人牙髓来源与人骨髓来源相比	人牙髓来源干细胞衍生外泌体的免疫调节活性更强
软骨再生	人脂肪来源与人滑膜液来源相比	在软骨再生方面，人脂肪来源间充质干细胞衍生外泌体是更好的microRNA-127-5p来源，可作为软骨再生治疗的强大候选者
神经溶解素活性	人脂肪来源与人骨髓来源相比	人脂肪来源间充质干细胞衍生外泌体具有更高的神经溶解素活性
血管生成	人脂肪来源与人骨髓来源相比	人脂肪来源间充质干细胞衍生外泌体与促血管生成高度相关

), ArticleFig(id=1246459866051661978, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, language=CN, label=表1, caption=

不同来源间充质干细胞衍生外泌体的不同作用

, figureFileSmall=null, figureFileBig=null, tableContent=

优势方面	不同来源间充质干细胞衍生的外泌体	结果
产量	人羊水来源与人骨髓来源相比	人羊水来源间充质干细胞衍生的外泌体产量更高
	犬骨髓来源与犬脂肪来源相比	犬骨髓来源间充质干细胞衍生的外泌体产量更高
组织修复能力	人脐带来源与人骨髓来源、人脂肪来源相比	人脐带来源间充质干细胞衍生的外泌体在组织修复能力上占有优势
免疫调节活性	人牙髓来源与人骨髓来源相比	人牙髓来源干细胞衍生外泌体的免疫调节活性更强
软骨再生	人脂肪来源与人滑膜液来源相比	在软骨再生方面，人脂肪来源间充质干细胞衍生外泌体是更好的microRNA-127-5p来源，可作为软骨再生治疗的强大候选者
神经溶解素活性	人脂肪来源与人骨髓来源相比	人脂肪来源间充质干细胞衍生外泌体具有更高的神经溶解素活性
血管生成	人脂肪来源与人骨髓来源相比	人脂肪来源间充质干细胞衍生外泌体与促血管生成高度相关

), ArticleFig(id=1246459866148130979, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=

方法	优点	缺点
超速离心	产量高，蛋白质污染水平较低	花费时间较长，需要大量样本
冲洗分离	纯度高、操作时间短、花费少	产量不足，在操作过程中会冲洗掉部分外泌体
沉淀	操作时间短	纯度低，容易受到污染
超滤	纯度高，可以减少被试剂污染的概率	增加、掺杂其他大小相似的颗粒
免疫亲和捕获	特异性高，可以提取到所需要的外泌体	产量低、昂贵、容易受到外界因素影响
微流控技术	操作方法简单、堵塞机器风险低	缺少试验
质谱法	纯度高、样品消耗少	缺乏标准化的分离标准

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间充质干细胞衍生外泌体的分离提取方法

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方法	优点	缺点
超速离心	产量高，蛋白质污染水平较低	花费时间较长，需要大量样本
冲洗分离	纯度高、操作时间短、花费少	产量不足，在操作过程中会冲洗掉部分外泌体
沉淀	操作时间短	纯度低，容易受到污染
超滤	纯度高，可以减少被试剂污染的概率	增加、掺杂其他大小相似的颗粒
免疫亲和捕获	特异性高，可以提取到所需要的外泌体	产量低、昂贵、容易受到外界因素影响
微流控技术	操作方法简单、堵塞机器风险低	缺少试验
质谱法	纯度高、样品消耗少	缺乏标准化的分离标准

), ArticleFig(id=1246459866320097459, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=

不同来源间充质干细胞衍生的外泌体	机制	结果	文献
人脐带来源	miR-3940-5p通过靶向ITGA6和转化生长因子β，抑制结直肠癌细胞的侵袭和上皮-间质转化	抑制结直肠癌的生长和转移	[58]
	通过诱导miR-1827靶向抑制SUCNR1的表达	抑制结直肠癌的发生及肝转移	[59]
	通过miR-431-5p下调过氧化物还原酶1的表达	延缓结直肠癌细胞的生长，抑制结直肠癌的进展	[60]
	通过miR-146a抑制SUMO1的表达	通过减轻结肠炎的恶化，减少了结肠炎转化为结直肠癌的概率	[61]
人骨髓来源	通过miR-16-5p下调ITGA2的表达	抑制结直肠癌细胞增殖、转移和侵袭	[62]
	通过miR-4461下调COPB2的表达	抑制结直肠癌的发生	[63]
	抑制基质金属蛋白酶2和基质金属蛋白酶9、SNAIL和TWIST的表达，通过miR-100/mTOR/miR-143轴诱导结直肠癌细胞凋亡	抑制结直肠癌细胞增殖、转移和侵袭	[64]
	通过miR-22-3p介导RAP2B/PI3K/AKT通路，对SW480细胞的增殖和侵袭有抑制作用	抑制结直肠癌的进展	[65]
	通过SCARA5抑制结直肠癌细胞中蛋白激酶B和磷酸肌醇3-激酶的磷酸化	抑制结直肠癌的进展	[66]
	成纤维细胞生长因子受体3的过度表达导致结直肠癌的进展，通过miR-99b-5p靶向成纤维细胞生长因子受体3来抑制肿瘤进展	抑制结直肠癌细胞增殖、转移和侵袭	[67]
人脂肪来源	抑制水通道蛋白5和表皮生长因子受体的表达	抑制结直肠癌的进展	[68]

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不同来源间充质干细胞衍生外泌体在治疗结直肠癌中的作用及机制

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不同来源间充质干细胞衍生的外泌体	机制	结果	文献
人脐带来源	miR-3940-5p通过靶向ITGA6和转化生长因子β，抑制结直肠癌细胞的侵袭和上皮-间质转化	抑制结直肠癌的生长和转移	[58]
	通过诱导miR-1827靶向抑制SUCNR1的表达	抑制结直肠癌的发生及肝转移	[59]
	通过miR-431-5p下调过氧化物还原酶1的表达	延缓结直肠癌细胞的生长，抑制结直肠癌的进展	[60]
	通过miR-146a抑制SUMO1的表达	通过减轻结肠炎的恶化，减少了结肠炎转化为结直肠癌的概率	[61]
人骨髓来源	通过miR-16-5p下调ITGA2的表达	抑制结直肠癌细胞增殖、转移和侵袭	[62]
	通过miR-4461下调COPB2的表达	抑制结直肠癌的发生	[63]
	抑制基质金属蛋白酶2和基质金属蛋白酶9、SNAIL和TWIST的表达，通过miR-100/mTOR/miR-143轴诱导结直肠癌细胞凋亡	抑制结直肠癌细胞增殖、转移和侵袭	[64]
	通过miR-22-3p介导RAP2B/PI3K/AKT通路，对SW480细胞的增殖和侵袭有抑制作用	抑制结直肠癌的进展	[65]
	通过SCARA5抑制结直肠癌细胞中蛋白激酶B和磷酸肌醇3-激酶的磷酸化	抑制结直肠癌的进展	[66]
	成纤维细胞生长因子受体3的过度表达导致结直肠癌的进展，通过miR-99b-5p靶向成纤维细胞生长因子受体3来抑制肿瘤进展	抑制结直肠癌细胞增殖、转移和侵袭	[67]
人脂肪来源	抑制水通道蛋白5和表皮生长因子受体的表达	抑制结直肠癌的进展	[68]

), ArticleFig(id=1246459866534006979, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=

不同来源间充质干细胞衍生的外泌体	机制	结果	文献
人脂肪来源	通过TRPC3/NF-κB轴诱导肿瘤相关成纤维细胞的表型	加速结肠癌的进展	[69]
人骨髓来源	通过miR-142-3p可以增加结肠癌中肿瘤干细胞的数量	加速结肠癌的进展	[70]
	通过AMPK/mTOR介导的NF-κB激活促进细胞的增殖、迁移和集落形成	诱导癌细胞的增加，促进结直肠癌的发生与转移	[71]
	通过miR-424促进结直肠癌细胞的增殖和迁移	诱导结直肠癌的发生与转移	[72]
癌症相关成纤维细胞	通过转移外泌体长链非编码RNA H19促进结肠癌干细胞增殖和增加化疗耐药性	加速癌细胞的增殖与分化，增加化疗耐药性	[73]
	外泌体长链非编码RNA LINC00659通过miR-342-3p/ANXA2轴促进结直肠癌细胞增殖	加速结肠癌的进展	[74]

), ArticleFig(id=1246459866643058891, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, language=CN, label=表4, caption=

不同来源间充质干细胞衍生外泌体可以作为治疗结直肠癌的潜在靶点

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不同来源间充质干细胞衍生的外泌体	机制	结果	文献
人脂肪来源	通过TRPC3/NF-κB轴诱导肿瘤相关成纤维细胞的表型	加速结肠癌的进展	[69]
人骨髓来源	通过miR-142-3p可以增加结肠癌中肿瘤干细胞的数量	加速结肠癌的进展	[70]
	通过AMPK/mTOR介导的NF-κB激活促进细胞的增殖、迁移和集落形成	诱导癌细胞的增加，促进结直肠癌的发生与转移	[71]
	通过miR-424促进结直肠癌细胞的增殖和迁移	诱导结直肠癌的发生与转移	[72]
癌症相关成纤维细胞	通过转移外泌体长链非编码RNA H19促进结肠癌干细胞增殖和增加化疗耐药性	加速癌细胞的增殖与分化，增加化疗耐药性	[73]
	外泌体长链非编码RNA LINC00659通过miR-342-3p/ANXA2轴促进结直肠癌细胞增殖	加速结肠癌的进展	[74]

), ArticleFig(id=1246459866735333584, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=

化疗药物	不同来源间充质干细胞衍生的外泌体	机制	结果	文献
铂类药物	人脂肪来源	通过miR-1236抑制SLC9A1和Wnt/β-Catenin信号传导	降低耐药性	[90]
	人骨髓来源	递送拮抗剂以增强对卡铂的敏感性，防止乳腺癌细胞休眠	降低耐药性	[91]
紫衫醇类药物	人脂肪来源	通过miR-146a体外调节LAMC2和PI3K/Akt信号通路	降低耐药性	[92]
		通过miR-451a抑制ADAM10的表达，抑制肝细胞性肝癌细胞的上皮-间充质转化	降低耐药性	[93]
阿霉素类药物	人骨髓来源	通过miR-21-5p增加乳腺癌细胞中的S100A6表达	增加耐药性	[94]
5-氟尿嘧啶	人脐带来源	通过激活CaM-Ks/Raf/MEK/ERK信号通路和上调多药耐药相关蛋白表达	增加耐药性	[95]

), ArticleFig(id=1246459866819219669, tenantId=1146029695717560320, journalId=1246415837536497731, articleId=1246459850427880022, language=CN, label=表5, caption=

间充质干细胞衍生外泌体对不同种类化疗药物耐药性的作用

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化疗药物	不同来源间充质干细胞衍生的外泌体	机制	结果	文献
铂类药物	人脂肪来源	通过miR-1236抑制SLC9A1和Wnt/β-Catenin信号传导	降低耐药性	[90]
	人骨髓来源	递送拮抗剂以增强对卡铂的敏感性，防止乳腺癌细胞休眠	降低耐药性	[91]
紫衫醇类药物	人脂肪来源	通过miR-146a体外调节LAMC2和PI3K/Akt信号通路	降低耐药性	[92]
		通过miR-451a抑制ADAM10的表达，抑制肝细胞性肝癌细胞的上皮-间充质转化	降低耐药性	[93]
阿霉素类药物	人骨髓来源	通过miR-21-5p增加乳腺癌细胞中的S100A6表达	增加耐药性	[94]
5-氟尿嘧啶	人脐带来源	通过激活CaM-Ks/Raf/MEK/ERK信号通路和上调多药耐药相关蛋白表达	增加耐药性	[95]

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