干细胞外泌体临床转化挑战与应对策略

doi:10.3877/cma.j.issn.2095-1221.2025.05.007

中华细胞与干细胞杂志(电子版) ›› 2025, Vol. 15 ›› Issue (05) : 301 -311. doi: 10.3877/cma.j.issn.2095-1221.2025.05.007

所属专题：文献；

综述

干细胞外泌体临床转化挑战与应对策略

丁琳¹^,²^,³^,⁴, 梁敏莉¹^,²^,³^,⁴, 钟嘉琪¹^,²^,³^,⁴, 李富荣¹^,²^,³^,⁴^,^†(

)

¹518020　深圳，南方科技大学第一附属医院（深圳市人民医院）转化医学协同创新中心
²518020　深圳市免疫细胞治疗公共服务平台
³518020　深圳，广东省干细胞与细胞治疗工程技术研究中心
⁴518020　深圳市干细胞研究与临床转化重点实验室

收稿日期:2025-07-01 出版日期:2025-10-01
通信作者: 李富荣
基金资助:
国家自然科学基金(32300784); 深圳市医学研究专项(A2403018); 深圳市科技计划资助(JCYJ20220818102605012); 国家重点研发计划(2022YFA1104900)

Challenges and coping strategies for the clinical translation of stem cell-derived exosomes

Lin Ding¹^,²^,³^,⁴, Minli Liang¹^,²^,³^,⁴, Jiaqi Zhong¹^,²^,³^,⁴, Furong Li¹^,²^,³^,⁴^,^†()

¹Center for Translational Medicine Collaborative Innovation, the First Affliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen 518020, China
²Shenzhen Immune Cell Therapy Public Service Platform, Shenzhen 518020, China
³Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen 518020, China
⁴Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen 518020, China

Received:2025-07-01 Published:2025-10-01
Corresponding author: Furong Li

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引用本文：

丁琳, 梁敏莉, 钟嘉琪, 李富荣. 干细胞外泌体临床转化挑战与应对策略[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(05): 301-311.

Lin Ding, Minli Liang, Jiaqi Zhong, Furong Li. Challenges and coping strategies for the clinical translation of stem cell-derived exosomes[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2025, 15(05): 301-311.

干细胞外泌体作为无细胞治疗方案，规避活细胞移植风险，具有更高生物安全性，且可通过工程化修饰增强组织靶向性和治疗效能，有望成为替代干细胞的新型治疗策略。针对如何提高干细胞外泌体产量、批次稳定性、治疗效能及活性维持等临床转化挑战，本综述提出3D培养联合永生化细胞系方案、开发工程化赋能外泌体系统及发展创新外泌体保存技术的应对策略。旨在进一步推动干细胞外泌体在标准化生产、治疗应用及长效储存的临床转化进程。

关键词: 干细胞, 外泌体, 临床转化, 工程化, 保存

Stem cell-derived exosomes, as a cell-free therapeutic approach, circumvent the risks associated with live cell transplantation and offer enhanced biological safety. Through engineering modifications, they can augment tissue targeting and therapeutic efficacy, making them a promising new treatment strategy that could potentially replace stem cells. In response to the clinical translation challenges, such as improving the yield, batch stability, therapeutic efficacy, and activity maintenance of stem cell-derived exosomes, this review proposes coping strategies including the use of 3D culture combined with immortalized cell lines, the development of engineered exosome empowerment systems, and innovative exosome preservation techniques aiming to further advance the clinical translation process of stem cell-derived exosomes in standardized production, therapeutic applications, and long-term storage.

Key words: Stem cells, Exosomes, Clinical translation, Engineering, Preservation

图1 干细胞外泌体疗法临床转化三大核心挑战及应对策略

表1 常用生物反应器类型及优缺点

生物反应器类型	核心结构/原理	关键优势	主要局限
搅拌式生物反应器	机械搅拌桨驱动培养液与微载体混合	混合效率高，均质性好；易联用微载体，兼容性强；支持高细胞密度（达1×10⁷个细胞/mL）	剪切力可能造成细胞损伤，需优化桨叶设计（如螺旋桨式）与转速控制策略
固定床式生物反应器	细胞贴附于多孔载体（如海绵状基质）内部生长	提供低剪切力环境，适合脆弱细胞（如神经干细胞）；载体稳定性高，利于长期培养	载体内部易形成营养/氧气梯度，导致深层细胞坏死风险升高；载体清洗与细胞回收困难
气升式生物反应器	底部通入气体驱动培养液循环（无机械搅拌）	剪切力极低，细胞存活率高；结构简单，不易污染	大规模培养时氧传输效率不足（气泡对氧溶解能力有限）；循环控制精度要求高
膜式生物反应器（中空纤维）	模拟毛细血管结构，利用选择性渗透膜实现物质交换	维持稳态微环境，保护细胞活性；高效回收高质量外泌体；工艺重复性好，易放大生产	膜污染可能导致通量下降，需定期维护；初始设备投资成本高

表1 常用生物反应器类型及优缺点

生物反应器类型	核心结构/原理	关键优势	主要局限
搅拌式生物反应器	机械搅拌桨驱动培养液与微载体混合	混合效率高，均质性好；易联用微载体，兼容性强；支持高细胞密度（达1×10⁷个细胞/mL）	剪切力可能造成细胞损伤，需优化桨叶设计（如螺旋桨式）与转速控制策略
固定床式生物反应器	细胞贴附于多孔载体（如海绵状基质）内部生长	提供低剪切力环境，适合脆弱细胞（如神经干细胞）；载体稳定性高，利于长期培养	载体内部易形成营养/氧气梯度，导致深层细胞坏死风险升高；载体清洗与细胞回收困难
气升式生物反应器	底部通入气体驱动培养液循环（无机械搅拌）	剪切力极低，细胞存活率高；结构简单，不易污染	大规模培养时氧传输效率不足（气泡对氧溶解能力有限）；循环控制精度要求高
膜式生物反应器（中空纤维）	模拟毛细血管结构，利用选择性渗透膜实现物质交换	维持稳态微环境，保护细胞活性；高效回收高质量外泌体；工艺重复性好，易放大生产	膜污染可能导致通量下降，需定期维护；初始设备投资成本高

表2 当前常用外泌体提取技术的原理及优缺点

分离方法	原理	优点	缺点
超速离心法	利用不同离心力分步去除细胞、碎片及大囊泡，最终高速沉淀外泌体	标准方法，适用大体积样本量；操作简单，无需特殊试剂	耗时较长；设备昂贵；外泌体易破损；不适用于微量样本
密度梯度离心法	在超速离心基础上，通过蔗糖/碘克沙醇形成密度梯度，利用外泌体与其他颗粒的密度差异进行分离	纯度高；有效去除蛋白污染	耗时较长；设备昂贵；回收率低；操作复杂
聚合物沉淀法	亲水聚合物与外泌体相结合，形成疏水层，降低其溶解度，低速离心即可沉淀	操作简单，无需超离设备；适用各类体积样本	蛋白质等杂质多；聚合物残留干扰下游分析
尺寸排阻色谱法	多孔凝胶柱按分子粒径尺寸分离，大分子外泌体先洗脱	保留完整结构与活性；纯度高，蛋白污染少	步骤繁琐，需多步离心、过滤；耗时长；柱材成本高、易堵塞；不适合大量样本处理
免疫亲和法	抗体修饰磁珠特异性结合外泌体表面标志物（如CD63/CD81）	特异性高，适合亚群研究；纯度高，降低蛋白等杂质干扰	抗体成本高；不适合大量样本处理；抗体结合可能损伤功能活性
超滤法	超滤膜截留外泌体，滤除小分子	成本低；耗时短；适用各类体积样本	纯度低；膜吸附和堵塞导致外泌体损失；剪切力致结构变形

表2 当前常用外泌体提取技术的原理及优缺点

分离方法	原理	优点	缺点
超速离心法	利用不同离心力分步去除细胞、碎片及大囊泡，最终高速沉淀外泌体	标准方法，适用大体积样本量；操作简单，无需特殊试剂	耗时较长；设备昂贵；外泌体易破损；不适用于微量样本
密度梯度离心法	在超速离心基础上，通过蔗糖/碘克沙醇形成密度梯度，利用外泌体与其他颗粒的密度差异进行分离	纯度高；有效去除蛋白污染	耗时较长；设备昂贵；回收率低；操作复杂
聚合物沉淀法	亲水聚合物与外泌体相结合，形成疏水层，降低其溶解度，低速离心即可沉淀	操作简单，无需超离设备；适用各类体积样本	蛋白质等杂质多；聚合物残留干扰下游分析
尺寸排阻色谱法	多孔凝胶柱按分子粒径尺寸分离，大分子外泌体先洗脱	保留完整结构与活性；纯度高，蛋白污染少	步骤繁琐，需多步离心、过滤；耗时长；柱材成本高、易堵塞；不适合大量样本处理
免疫亲和法	抗体修饰磁珠特异性结合外泌体表面标志物（如CD63/CD81）	特异性高，适合亚群研究；纯度高，降低蛋白等杂质干扰	抗体成本高；不适合大量样本处理；抗体结合可能损伤功能活性
超滤法	超滤膜截留外泌体，滤除小分子	成本低；耗时短；适用各类体积样本	纯度低；膜吸附和堵塞导致外泌体损失；剪切力致结构变形

表3 近期外泌体提取纯化创新技术

技术名称	核心原理/技术	关键优势	应用场景/特点
超声纳滤技术（EXODUS系统，汇芯生物）	负压振荡+双耦合超声振荡作用于纳米超滤芯片，快速去除游离核酸/蛋白杂质并截留外泌体	全自动操作；支持微量样本（泪液、脑脊液）至规模化样本提取；杂蛋白去除效率> 99%；回收率> 90%	适用于需要高纯度、高回收率且样本量波动大的研究或临床场景
Cytiva^TM superSEC填料（切向流联用，Cytiva公司）	高分辨率尺寸排阻层析+优化流体动力学设计，结合切向流富集	缩短层析循环时间；提升杂质去除效率；纯度指数高于传统填料（如Sepharose^TM CL-2B）	为外泌体规模化生产与临床应用提供可靠解决方案（如生物制药级外泌体纯化）
微流控技术^[47,48]	分离型：双切向流+两种孔径纳米多孔膜；检测型：化学发光检测+杂交链反应	微量样本处理（如临床少量血液）、高活性外泌体获取；高灵敏度外泌体多靶标miRNA检测	适用于临床即时诊断（如肿瘤标志物外泌体快速检测）、微量样本的高精准分离
细胞内泌体提取^[49,50]	低温"冷萃"裂解DPSCs细胞，直接分离内泌体	提取效率是外泌体的16倍；碱性成纤维细胞生长因子、脑源性神经营养因子、表皮生长因子受体等生长因子含量高于外泌体；低成本、操作简单	为细胞囊泡高效提取提供新思路（如干细胞来源囊泡的低成本制备），适用于再生医学研究

表3 近期外泌体提取纯化创新技术

技术名称	核心原理/技术	关键优势	应用场景/特点
超声纳滤技术（EXODUS系统，汇芯生物）	负压振荡+双耦合超声振荡作用于纳米超滤芯片，快速去除游离核酸/蛋白杂质并截留外泌体	全自动操作；支持微量样本（泪液、脑脊液）至规模化样本提取；杂蛋白去除效率> 99%；回收率> 90%	适用于需要高纯度、高回收率且样本量波动大的研究或临床场景
Cytiva^TM superSEC填料（切向流联用，Cytiva公司）	高分辨率尺寸排阻层析+优化流体动力学设计，结合切向流富集	缩短层析循环时间；提升杂质去除效率；纯度指数高于传统填料（如Sepharose^TM CL-2B）	为外泌体规模化生产与临床应用提供可靠解决方案（如生物制药级外泌体纯化）
微流控技术^[47,48]	分离型：双切向流+两种孔径纳米多孔膜；检测型：化学发光检测+杂交链反应	微量样本处理（如临床少量血液）、高活性外泌体获取；高灵敏度外泌体多靶标miRNA检测	适用于临床即时诊断（如肿瘤标志物外泌体快速检测）、微量样本的高精准分离
细胞内泌体提取^[49,50]	低温"冷萃"裂解DPSCs细胞，直接分离内泌体	提取效率是外泌体的16倍；碱性成纤维细胞生长因子、脑源性神经营养因子、表皮生长因子受体等生长因子含量高于外泌体；低成本、操作简单	为细胞囊泡高效提取提供新思路（如干细胞来源囊泡的低成本制备），适用于再生医学研究

图2 外泌体工程化改造策略（本图由Figdraw绘制）

图3 外泌体质量控制五维体系

1	闫永利, 叶进培. hESC衍生间充质干细胞可显著促进体外血管生成[J]. 中国细胞生物学学报, 2021, 43(8):1561-1573.
2	Hughey CC, Ma LL, James FD, et al. Mesenchymal stem cell transplantation for the infarcted heart: therapeutic potential for insulin resistance beyond the heart[J]. Cardiovasc Diabetol, 2013, 12:128.
3	Ringdén O, Uzunel M, Rasmusson I, et al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease[J]. Transplantation, 2006, 81(10):1390-1397.
4	Zeng LT, Liu C, Wu Y, et al. Efficacy and safety of mesenchymal stromal cell transplantation in the treatment of autoimmune and rheumatic immune diseases:a systematic review and meta-analysis of randomized controlled trials[J]. Stem Cell Res Ther, 2025, 16(1):65.
5	Datta N. Stem cell therapy for SARS-CoV-2 and influenza virus infections[J]. BIO Integration, 2024, 5(1):1-13.
6	Huang XS, Wang Y, Yan W, et al. Production of gene-corrected adult beta globin protein in human erythrocytes differentiated from patient iPSCs after genome editing of the sickle point mutation[J]. Stem Cells, 2015, 33(5):1470-1479.
7	Liu N, Matsumura H, Kato T, et al. Stem cell competition orchestrates skin homeostasis and ageing[J]. Nature, 2019, 568(7752):344-350.
8	Mejia-Ramirez E, Geiger H, Florian MC. Loss of epigenetic polarity is a hallmark of hematopoietic stem cell aging[J]. Hum Mol Genet, 2020, 29(R2):R248-R254.
9	Bolton EM, Bradley JA. Avoiding immunological rejection in regenerative medicine[J]. Regen Med, 2015, 10(3):287-304.
10	Andersen MS, Jensen KB. Stem cell heterogeneity revealed[J]. Nat Cell Biol, 2016, 18(6):587-589.
11	Cao Q, Zhang R,Ye Q. Association and enterprise standard for producing and monitoring of quality extracellular vesicles/exosomes derived from human mesenchymal stem cells[J]. Nano Trans Med, 2024, 3:100058.
12	Tan F, Li XR, Wang Z, et al. Clinical applications of stem cell-derived exosomes[J]. Signal Transduct Target Ther, 2024, 9(1):17.
13	Li LY, Wang F, Zhu DS, et al. Engineering exosomes and exosome-like nanovesicles for improving tissue targeting and retention[J]. Fundam Res, 2025, 5(2):851-867.
14	Xing YH, Ren XS, Li DH, et al. Exosome separation and analysis based on microfluidics technology and its clinical applications[J]. Se Pu, 2025, 43(5):455-471.
15	叶青松, 彭友俭, 骆瑜. 细胞外泌体的分离提取标准化及临床转化进展[J]. 口腔疾病防治, 2022, 30(9):609-619.
16	Gelibter S, Marostica G, Mandelli A, et al. The impact of storage on extracellular vesicles: a systematic study[J]. J Extracell Vesicles, 2022, 11(2):e12162.
17	van de Wakker SI, Meijers FM, Sluijter JPG, et al. Extracellular vesicle heterogeneity and its impact for regenerative medicine applications[J]. Pharmacol Rev, 2023, 75(5):1043-1061.
18	Li CY, Wu XY, Tong JB, et al. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy[J]. Stem Cell Res Ther, 2015, 6(1):55.
19	Amable PR, Teixeira MVT, Carias RBV, et al. Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton's jelly[J]. Stem Cell Res Ther, 2014, 5(2):53.
20	Kirkham AM, Bailey AJM, Tieu A, et al. MSC-derived extracellular vesicles in preclinical animal models of bone injury: a systematic review and meta-analysis[J]. Stem Cell Rev Rep, 2022, 18(3):1054-1066.
21	Shi LY, Ye XC, Zhou J, et al. Roles of DNA methylation in influencing the functions of dental-derived mesenchymal stem cells[J]. Oral Dis, 2024, 30(5):2797-2806.
22	Almeria C, Kress S, Weber V, et al. Heterogeneity of mesenchymal stem cell-derived extracellular vesicles is highly impacted by the tissue/cell source and culture conditions[J]. Cell Biosci, 2022, 12(1):51.
23	Chen XL, Chen A, Woo TL, et al. Investigations into the metabolism of two-dimensional colony and suspended microcarrier cultures of human embryonic stem cells in serum-free media[J]. Stem Cells Dev, 2010, 19(11):1781-1792.
24	Tapp H, Deepe R, Ingram JA, et al. Adipose-derived mesenchymal stem cells from the sand rat: transforming growth factor beta and 3D co-culture with human disc cells stimulate proteoglycan and collagen type I rich extracellular matrix[J]. Arthritis Res Ther, 2008, 10(4):R89.
25	Park W, Jang S, Kim TW, et al. Microfluidic-printed microcarrier for in vitro expansion of adherent stem cells in 3D culture platform[J]. Macromol Biosci, 2019, 19(8):e1900136.
26	Wang X, Ouyang LM, Chen WX, et al. Efficient expansion and delayed senescence of hUC-MSCs by microcarrier-bioreactor system[J]. Stem Cell Res Ther, 2023, 14(1):284.
27	王晓勋, 张中. 不同微载体细胞培养技术在生物制品领域的应用[J]. 中国生物制品学杂志, 2023, 36(12):1515.
28	Yan XJ, Zhang K, Yang YP, et al. Dispersible and dissolvable porous microcarrier tablets enable efficient large-scale human mesenchymal stem cell expansion[J]. Tissue Eng Part C Methods, 2020, 26(5):263-275.
29	Feng L, Liang SJ, Zhou YY, et al. Three-dimensional printing of hydrogel scaffolds with hierarchical structure for scalable stem cell culture[J]. ACS Biomater Sci Eng, 2020, 6(5):2995-3004.
30	Haraszti RA, Miller R, Stoppato M, et al. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity[J]. Mol Ther, 2018, 26(12):2838-2847.
31	Yan LT, Wu X. Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity[J]. Cell Biol Toxicol, 2020, 36(2):165-178.
32	Kronstadt SM, Patel DB, Born LJ, et al. Mesenchymal stem cell culture within perfusion bioreactors incorporating 3D-printed scaffolds enables improved extracellular vesicle yield with preserved bioactivity[J]. Adv Healthc Mater, 2023, 12(20):e2300584.
33	Mi LY, Hu JP, Li N, et al. The mechanism of stem cell aging[J]. Stem Cell Rev Rep, 2022, 18(4):1281-1293.
34	Simonsen JL, Rosada C, Serakinci N, et al. Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells[J]. Nat Biotechnol, 2002, 20(6):592-596.
35	Ahuja D, Sáenz-Robles MT, Pipas JM. SV40 large T antigen targets multiple cellular pathways to elicit cellular transformation[J]. Oncogene, 2005, 24(52):7729-7745.
36	陈冬雪, 白喜龙, 梁英民. SV40-LT基因使牙髓干细胞永生化的研究[J]. 实用口腔医学杂志, 2022, 38(2):189-193.
37	Michael S, Lambert PF, Strati K. The HPV16 oncogenes cause aberrant stem cell mobilization[J]. Virology, 2013, 443(2):218-225.
38	Yamaguchi N, Horio E, Sonoda J, et al. Immortalization of mesenchymal stem cells for application in regenerative medicine and their potential risks of tumorigenesis[J]. Int J Mol Sci, 2024, 25(24):13562.
39	Basalova N, Sagaradze G, Arbatskiy M, et al. Secretome of mesenchymal stromal cells prevents myofibroblasts differentiation by transferring fibrosis-associated microRNAs within extracellular vesicles[J]. Cells, 2020, 9(5):1272.
40	Kraskiewicz H, Paprocka M, Bielawska-Pohl A, et al. Can supernatant from immortalized adipose tissue MSC replace cell therapy? An in vitro study in chronic wounds model[J]. Stem Cell Res Ther, 2020, 11(1):29.
41	Guo SW, Debbi L, Zohar B, et al. Stimulating extracellular vesicles production from engineered tissues by mechanical forces[J]. Nano Lett, 2021, 21(6):2497-2504.
42	Wang JL, Bonacquisti EE, Brown AD, et al. Boosting the biogenesis and secretion of mesenchymal stem cell-derived exosomes[J]. Cells, 2020, 9(3):660.
43	Fukuta T, Nishikawa A, Kogure K. Low level electricity increases the secretion of extracellular vesicles from cultured cells[J]. Biochem Biophys Rep, 2019, 21:100713.
44	Gonzalez-King H, García NA, Ontoria-Oviedo I, et al. Hypoxia inducible factor-1α potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes[J]. Stem Cells, 2017, 35(7):1747-1759.
45	Avnet S, Lemma S, Cortini M, et al. The release of inflammatory mediators from acid-stimulated mesenchymal stromal cells favours tumour invasiveness and metastasis in osteosarcoma[J]. Cancers (Basel), 2021, 13(22):5855.
46	李帅,刘亚婷, 仰大勇. 外泌体分离技术研究进展[J]. 化学学报, 2025, 83(4):428-438.
47	Hua X, Zhu Q, Liu Y, et al. A double tangential flow filtration-based microfluidic device for highly efficient separation and enrichment of exosomes[J]. Anal Chim Acta, 2023, 1258:341160.
48	Peng J, Li BC, Ma ZY, et al. A microfluidic-based chemiluminescence biosensor for sensitive multiplex detection of exosomal microRNAs based on hybridization chain reaction[J]. Talanta, 2025, 281:126838.
49	Duan XX, Zhang R, Feng HX, et al. A new subtype of artificial cell-derived vesicles from dental pulp stem cells with the bioequivalence and higher acquisition efficiency compared to extracellular vesicles[J]. J Extracell Vesicles, 2024, 13(7):e12473.
50	Ye Q, Zhang R. Intracellular vesicles: novel nanovesicles superior to extracellular vesicles in translational medicine and clinical applications[J]. Nano TransMed, 2024, 3:100044.
51	Hung ME, Leonard JN. Stabilization of exosome-targeting peptides via engineered glycosylation[J]. J Biol Chem, 2015, 290(13):8166-8172.
52	Yu YH, Li W, Mao L, et al. Genetically engineered exosomes display RVG peptide and selectively enrich a neprilysin variant: a potential formulation for the treatment of Alzheimer's disease[J]. J Drug Target, 2021, 29(10):1128-1138.
53	Zheng WY, He R, Liang XM, et al. Cell-specific targeting of extracellular vesicles though engineering the glycocalyx[J]. J Extracell Vesicles, 2022, 11(12):e12290.
54	Du W, Chen C, Liu YY, et al. A combined "eat me/don't eat me" strategy based on exosome for acute liver injury treatment[J]. Cell Rep Med, 2025, 6(4):102033.
55	Geng TJ, Leung E, Chamley LW, et al. Functionalisation of extracellular vesicles with cyclic-RGDyC potentially for glioblastoma targeted intracellular drug delivery[J]. Biomater Adv, 2023, 149:213388.
56	Fan YY, Zhou YS, Lu M, et al. Responsive dual-targeting exosome as a drug carrier for combination cancer immunotherapy[J]. Research, 2021, 2021:9862876.
57	Zhan Q, Yi KK, Qi HZ, et al. Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy[J]. Theranostics, 2020, 10(17):7889-7905.
58	Zhou JL, Wang YH, Zhang LZ, et al. Engineered exosomes-mediated transfer of hsa-miR-320a overcomes chemoresistance in cervical cancer cells via targeting MCL1[J]. Front Pharmacol, 2022, 13:883445.
59	Huang JH, Yu MY, Yin WJ, et al. Development of a novel RNAi therapy: Engineered miR-31 exosomes promoted the healing of diabetic wounds[J]. Bioact Mater, 2021, 6(9):2841-2853.
60	Shi Y, Wang S, Liu DW, et al. Exosomal miR-4645-5p from hypoxic bone marrow mesenchymal stem cells facilitates diabetic wound healing by restoring keratinocyte autophagy[J]. Burns Trauma, 2024, 12:tkad058.
61	Chen W, Yang MC, Bai J, et al. Exosome-modified tissue engineered blood vessel for endothelial progenitor cell capture and targeted siRNA delivery[J]. Macromol Biosci, 2018, 18(2):1700242.
62	Hao R, Yu ZT, Du J, et al. A high-throughput nanofluidic device for exosome nanoporation to develop cargo delivery vehicles[J]. Small, 2021, 17(35):e2102150.
63	Son G, Song J, Park JC, et al. Fusogenic lipid nanoparticles for rapid delivery of large therapeutic molecules to exosomes[J]. Nat Commun, 2025, 16(1):4799.
64	Görgens A, Corso G, Hagey DW, et al. Identification of storage conditions stabilizing extracellular vesicles preparations[J]. J Extracell Vesicles, 2022, 11(6):e12238.
65	Wu JY, Li YJ, Hu XB, et al. Preservation of small extracellular vesicles for functional analysis and therapeutic applications: a comparative evaluation of storage conditions[J]. Drug Deliv, 2021, 28(1):162-170.
66	Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines[J]. J Extracell Vesicles, 2018, 7(1):1535750.
67	高雪, 慈小燕, 张英驰, 等. 间充质干细胞来源外泌体的分离及贮存方法研究进展[J]. 药物评价研究, 2024, 47(5):1146-1152.
68	吴颖杰, 耿梦缘, 汪晶, 等. 不同冻干保护剂在外泌体储存中的研究[J]. 天津医科大学学报, 2022, 28(4):353-359.
69	Ji R, Wang HL, Zheng X, et al. Tetraspanin 4 mediates cholesterol-dependent exosome membrane protection from cryodamage[J]. Nano Lett, 2025, 25(27):10722-10732.

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Challenges and coping strategies for the clinical translation of stem cell-derived exosomes

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Challenges and coping strategies for the clinical translation of stem cell-derived exosomes