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Nano Research 2023, 16(5): 6991-7006 https://doi.org/10.1007/s12274-022-5275-5
Review Article | Issue | Published: 27 December 2022

Native and engineered exosomes for inflammatory disease

Show Author's Information Xiaoyi Ma§,  Bingbing Liu§,  Limin Fan,  Yiqiong Liu,  Yuge Zhao,  Tianbin Ren( ),  Yan Li( ),  Yongyong Li( )
Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China

§ Xiaoyi Ma and Bingbing Liu contributed equally to this work.

Keywords:
inflammation, exosome, engineered exosome, exosomes-based therapy
Topics:
Cell engineering
Cite this article:
Ma X, Liu B, Fan L, et al. Native and engineered exosomes for inflammatory disease. Nano Research, 2023, 16(5): 6991-7006. https://doi.org/10.1007/s12274-022-5275-5
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Abstract Full text About this article

Exosomes are extracellular vesicles which carry specific molecular information from donor cells and act as an intercellular communication vehicle, which have emerged as a novel cell-free strategy for the treatment of many diseases including inflammatory disease. Recently, rising studies have developed exosome-based strategies for novel inflammation therapy due to their biocompatibility and bioactivity. Researchers not only use native exosomes as therapeutic agents for inflammation, but also strive to make up for the natural defects of exosomes through engineering methods to improve and update the property of exosomes for enhanced therapeutic effects. The engineered exosomes can improve cargo-loading efficiency, targeting ability, stability, etc., to achieve combined and diverse treatment strategies in inflammation diseases. Herein, a comprehensive overview of the recent advances in application studies of native and engineered exosomes as well as the engineered methods is provided. Meanwhile, potential application prospects, possible challenges, and the development of clinical researches of exosome treatment strategy are concluded from plentiful examples, which may be able to provide guidance and suggestions for the future research and application of exosomes.


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About this article

Native and engineered exosomes for inflammatory disease

Show Author's information Xiaoyi Ma§, Bingbing Liu§, Limin Fan, Yiqiong Liu, Yuge Zhao, Tianbin Ren( ), Yan Li( ), Yongyong Li( )
Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China

§ Xiaoyi Ma and Bingbing Liu contributed equally to this work.

Abstract

Exosomes are extracellular vesicles which carry specific molecular information from donor cells and act as an intercellular communication vehicle, which have emerged as a novel cell-free strategy for the treatment of many diseases including inflammatory disease. Recently, rising studies have developed exosome-based strategies for novel inflammation therapy due to their biocompatibility and bioactivity. Researchers not only use native exosomes as therapeutic agents for inflammation, but also strive to make up for the natural defects of exosomes through engineering methods to improve and update the property of exosomes for enhanced therapeutic effects. The engineered exosomes can improve cargo-loading efficiency, targeting ability, stability, etc., to achieve combined and diverse treatment strategies in inflammation diseases. Herein, a comprehensive overview of the recent advances in application studies of native and engineered exosomes as well as the engineered methods is provided. Meanwhile, potential application prospects, possible challenges, and the development of clinical researches of exosome treatment strategy are concluded from plentiful examples, which may be able to provide guidance and suggestions for the future research and application of exosomes.

Keywords: inflammation, exosome, engineered exosome, exosomes-based therapy

References(176)

[1]

Medzhitov, R. The spectrum of inflammatory responses. Science 2021, 374, 1070–1075.
DOI Google Scholar
[2]

Schett, G.; Neurath, M. F. Resolution of chronic inflammatory disease: Universal and tissue-specific concepts. Nat. Commun. 2018, 9, 3261.
DOI Google Scholar
[3]

López-Campos, J. L.; Tan, W.; Soriano, J. B. Global burden of COPD. Respirology 2016, 21, 14–23.
DOI Google Scholar
[4]

Nakase, H.; Uchino, M.; Shinzaki, S.; Matsuura, M.; Matsuoka, K.; Kobayashi, T.; Saruta, M.; Hirai, F.; Hata, K.; Hiraoka, S. et al. Evidence-based clinical practice guidelines for inflammatory bowel disease 2020. J. Gastroenterol. 2021, 56, 489–526.
DOI Google Scholar
[5]

Fullerton, J. N.; Gilroy, D. W. Resolution of inflammation: A new therapeutic frontier. Nat. Rev. Drug Discov. 2016, 15, 551–567.
DOI Google Scholar
[6]

Bacchi, S.; Palumbo, P.; Sponta, A.; Coppolino, M. F. Clinical pharmacology of non-steroidal anti-inflammatory drugs: A review. Antiinflamm. Antiallergy Agents Med. Chem. 2012, 11, 52–64.
DOI Google Scholar
[7]

Eccleston, C.; Cooper, T. E.; Fisher, E.; Anderson, B.; Wilkinson, N. M. R. Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents. Cochrane Database Syst. Rev. 2017, 8, CD012537.
DOI Google Scholar
[8]

Tahamtan, A.; Teymoori-Rad, M.; Nakstad, B.; Salimi, V. Anti-inflammatory microRNAs and their potential for inflammatory diseases treatment. Front. Immunol. 2018, 9, 1377.
DOI Google Scholar
[9]

Lu, R. M.; Hwang, Y. C.; Liu, I. J.; Lee, C. C.; Tsai, H. Z.; Li, H. J.; Wu, H. C. Development of therapeutic antibodies for the treatment of diseases. J. Biomed. Sci. 2020, 27, 1.
DOI Google Scholar
[10]

Regmi, S.; Pathak, S.; Kim, J. O.; Yong, C. S.; Jeong, J. H. Mesenchymal stem cell therapy for the treatment of inflammatory diseases: Challenges, opportunities, and future perspectives. Eur. J. Cell Biol. 2019, 98, 151041.
DOI Google Scholar
[11]

Wiklander, O. P. B.; Brennan, M. Á.; Lötvall, J.; Breakefield, X. O.; El Andaloussi, S. Advances in therapeutic applications of extracellular vesicles. Sci. Transl. Med. 2019, 11, eaav8521.
DOI Google Scholar
[12]

Tkach, M.; Théry, C. Communication by extracellular vesicles: Where we are and where we need to go. Cell 2016, 164, 1226–1232.
DOI Google Scholar
[13]

Lee, B. C.; Kang, I.; Yu, K. R. Therapeutic features and updated clinical trials of mesenchymal stem cell (MSC)-derived exosomes. J. Clin. Med. 2021, 10, 711.
DOI Google Scholar
[14]

Sancho-Albero, M.; Navascués, N.; Mendoza, G.; Sebastián, V.; Arruebo, M.; Martín-Duque, P.; Santamaría, J. Exosome origin determines cell targeting and the transfer of therapeutic nanoparticles towards target cells. J. Nanobiotechnol. 2019, 17, 16.
DOI Google Scholar
[15]

Hade, M. D.; Suire, C. N.; Suo, Z. C. Mesenchymal stem cell-derived exosomes: Applications in regenerative medicine. Cells 2021, 10, 1959.
DOI Google Scholar
[16]

Zhou, L. Y.; Shen, M. Y.; Fan, X. L.; Liu, Y. F.; Yang, L. Pathogenic and potential therapeutic roles of exosomes derived from immune cells in liver diseases. Front. Immunol. 2022, 13, 810300.
DOI Google Scholar
[17]

Gupta, D.; Wiklander, O. P. B.; Görgens, A.; Conceição, M.; Corso, G.; Liang, X. M.; Seow, Y.; Balusu, S.; Feldin, U.; Bostancioglu, B. et al. Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles. Nat. Biomed. Eng. 2021, 5, 1084–1098.
DOI Google Scholar
[18]

Wozniak, A. L.; Adams, A.; King, K. E.; Dunn, W.; Christenson, L. K.; Hung, W. T.; Weinman, S. A. The RNA binding protein FMR1 controls selective exosomal miRNA cargo loading during inflammation. J. Cell Biol. 2020, 219, e201912074.
DOI Google Scholar
[19]

Li, X.; Li, C. Y.; Zhang, L. P.; Wu, M.; Cao, K.; Jiang, F. F.; Chen, D. X.; Li, N.; Li, W. H. The significance of exosomes in the development and treatment of hepatocellular carcinoma. Mol. Cancer 2020, 19, 1.
DOI Google Scholar
[20]

Skokos, D.; Botros, H. G.; Demeure, C.; Morin, J.; Peronet, R.; Birkenmeier, G.; Boudaly, S.; Mécheri, S. Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo. J. Immunol. 2003, 170, 3037–3045.
DOI Google Scholar
[21]

Banks, W. A.; Sharma, P.; Bullock, K. M.; Hansen, K. M.; Ludwig, N.; Whiteside, T. L. Transport of extracellular vesicles across the blood–brain barrier: Brain pharmacokinetics and effects of inflammation. Int. J. Mol. Sci. 2020, 21, 4407.
DOI Google Scholar
[22]

Hong, Y.; Nam, G. H.; Koh, E.; Jeon, S.; Kim, G. B.; Jeong, C.; Kim, D. H.; Yang, Y.; Kim, I. S. Exosome as a vehicle for delivery of membrane protein therapeutics, PH20, for enhanced tumor penetration and antitumor efficacy. Adv. Funct. Mater. 2018, 28, 1703074.
DOI Google Scholar
[23]

Samanta, S.; Rajasingh, S.; Drosos, N.; Zhou, Z. G.; Dawn, B.; Rajasingh, J. Exosomes: New molecular targets of diseases. Acta Pharmacol. Sin. 2018, 39, 501–513.
DOI Google Scholar
[24]

Fu, S. Y.; Wang, Y.; Xia, X. H.; Zheng, J. C. Exosome engineering: Current progress in cargo loading and targeted delivery. NanoImpact 2020, 20, 100261.
DOI Google Scholar
[25]

Dominici, M.; Le Blanc, K.; Mueller, I.; Slaper-Cortenbach, I.; Marini, F. C.; Krause, D. S.; Deans, R. J.; Keating, A.; Prockop, D. J.; Horwitz, E. M. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 2006, 8, 315–317.
DOI Google Scholar
[26]

Song, N.; Scholtemeijer, M.; Shah, K. Mesenchymal stem cell immunomodulation: Mechanisms and therapeutic potential. Trends Pharmacol. Sci. 2020, 41, 653–664.
DOI Google Scholar
[27]

Chen, Y.; Shao, J. Z.; Xiang, L. X.; Dong, X. J.; Zhang, G. R. Mesenchymal stem cells: A promising candidate in regenerative medicine. Int. J. Biochem. Cell Biol. 2008, 40, 815–820.
DOI Google Scholar
[28]

Galipeau, J.; Sensébé, L. Mesenchymal stromal cells: Clinical challenges and therapeutic opportunities. Cell Stem Cell 2018, 22, 824–833.
DOI Google Scholar
[29]

Zhou, X. N.; Kalluri, R. Biology and therapeutic potential of mesenchymal stem cell-derived exosomes. Cancer Sci. 2020, 111, 3100–3110.
DOI Google Scholar
[30]

Tang, Y. Y.; Zhou, Y.; Li, H. J. Advances in mesenchymal stem cell exosomes: A review. Stem Cell Res. Ther. 2021, 12, 71.
DOI Google Scholar
[31]

Di Nicola, M.; Carlo-Stella, C.; Magni, M.; Milanesi, M.; Longoni, P. D.; Matteucci, P.; Grisanti, S.; Gianni, A. M. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002, 99, 3838–3843.
DOI Google Scholar
[32]

Mosna, F.; Sensebé, L.; Krampera, M. Human bone marrow and adipose tissue mesenchymal stem cells: A user’s guide. Stem Cells Dev. 2010, 19, 1449–1470.
DOI Google Scholar
[33]

Vonk, L. A.; van Dooremalen, S. F. J.; Liv, N.; Klumperman, J.; Coffer, P. J.; Saris, D. B. F.; Lorenowicz, M. J. Mesenchymal stromal/stem cell-derived extracellular vesicles promote human cartilage regeneration in vitro. Theranostics 2018, 8, 906–920.
DOI Google Scholar
[34]

He, L.; He, T. W.; Xing, J. H.; Zhou, Q.; Fan, L.; Liu, C.; Chen, Y. Y.; Wu, D. P.; Tian, Z. M.; Liu, B. et al. Bone marrow mesenchymal stem cell-derived exosomes protect cartilage damage and relieve knee osteoarthritis pain in a rat model of osteoarthritis. Stem Cell Res. Ther. 2020, 11, 276.
DOI Google Scholar
[35]

Wang, N.; Liu, X. C.; Tang, Z.; Wei, X. H.; Dong, H.; Liu, Y. C.; Wu, H.; Wu, Z. G.; Li, X. K.; Ma, X. et al. Increased BMSC exosomal miR-140-3p alleviates bone degradation and promotes bone restoration by targeting Plxnb1 in diabetic rats. J. Nanobiotechnol. 2022, 20, 97.
DOI Google Scholar
[36]

Liu, H. S.; Liang, Z. X.; Wang, F. W.; Zhou, C.; Zheng, X. B.; Hu, T.; He, X. W.; Wu, X. R.; Lan, P. Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism. JCI Insight 2019, 4, e131273.
DOI Google Scholar
[37]

Cao, L.; Xu, H. X.; Wang, G.; Liu, M.; Tian, D. A.; Yuan, Z. L. Extracellular vesicles derived from bone marrow mesenchymal stem cells attenuate dextran sodium sulfate-induced ulcerative colitis by promoting M2 macrophage polarization. Int. Immunopharmacol. 2019, 72, 264–274.
DOI Google Scholar
[38]

Teng, X. M.; Chen, L.; Chen, W. Q.; Yang, J. J.; Yang, Z. Y.; Shen, Z. Y. Mesenchymal stem cell-derived exosomes improve the microenvironment of infarcted myocardium contributing to angiogenesis and anti-inflammation. Cell. Physiol. Biochem. 2015, 37, 2415–2424.
DOI Google Scholar
[39]

Firoozi, S.; Pahlavan, S.; Ghanian, M. H.; Rabbani, S.; Barekat, M.; Nazari, A.; Pakzad, M.; Shekari, F.; Hassani, S. N.; Moslem, F. et al. Mesenchymal stem cell-derived extracellular vesicles alone or in conjunction with a SDKP-conjugated self-assembling peptide improve a rat model of myocardial infarction. Biochem. Biophys. Res. Commun. 2020, 524, 903–909.
DOI Google Scholar
[40]

He, X. N.; Dong, Z. W.; Cao, Y. N.; Wang, H.; Liu, S. Y.; Liao, L.; Jin, Y.; Yuan, L.; Li, B. MSC-derived exosome promotes M2 polarization and enhances cutaneous wound healing. Stem Cells Int. 2019, 2019, 7132708.
DOI Google Scholar
[41]

Losurdo, M.; Pedrazzoli, M.; D'Agostino, C.; Elia, C. A.; Massenzio, F.; Lonati, E.; Mauri, M.; Rizzi, L.; Molteni, L.; Bresciani, E. et al. Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer’s disease. Stem Cells Transl. Med. 2020, 9, 1068–1084.
DOI Google Scholar
[42]

Ni, H. Q.; Yang, S.; Siaw-Debrah, F.; Hu, J. N.; Wu, K.; He, Z. B.; Yang, J. J.; Pan, S. S.; Lin, X.; Ye, H. T. et al. Exosomes derived from bone mesenchymal stem cells ameliorate early inflammatory responses following traumatic brain injury. Front. Neurosci. 2019, 13, 14.
DOI Google Scholar
[43]

Sisa, C.; Kholia, S.; Naylor, J.; Herrera Sanchez, M. B.; Bruno, S.; Deregibus, M. C.; Camussi, G.; Inal, J. M.; Lange, S.; Hristova, M. Mesenchymal stromal cell derived extracellular vesicles reduce hypoxia-ischaemia induced perinatal brain injury. Front. Physiol. 2019, 10, 282.
DOI Google Scholar
[44]

Parekkadan, B.; van Poll, D.; Suganuma, K.; Carter, E. A.; Berthiaume, F.; Tilles, A. W.; Yarmush, M. L. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS One 2007, 2, e941.
DOI Google Scholar
[45]

Zhang, Y. W.; Zhang, X. F.; Zhang, H. J.; Song, P.; Pan, W. M.; Xu, P.; Wang, G. L.; Hu, P.; Wang, Z. X.; Huang, K. P. et al. Mesenchymal stem cells derived extracellular vesicles alleviate traumatic hemorrhagic shock induced hepatic injury via IL-10/PTPN22-Mediated M2 kupffer cell polarization. Front. Immunol. 2022, 12, 811164.
DOI Google Scholar
[46]

Collino, F.; Bruno, S.; Incarnato, D.; Dettori, D.; Neri, F.; Provero, P.; Pomatto, M.; Oliviero, S.; Tetta, C.; Quesenberry, P. J. et al. AKI recovery induced by mesenchymal stromal cell-derived extracellular vesicles carrying MicroRNAs. J. Am. Soc. Nephrol. 2015, 26, 2349–2360.
DOI Google Scholar
[47]

Pollard, C. A.; Morran, M. P.; Nestor-Kalinoski, A. L. The COVID-19 pandemic: A global health crisis. Physiol. Genomics 2020, 52, 549–557.
DOI Google Scholar
[48]

Desterke, C.; Griscelli, F.; Imeri, J.; Marcoux, P.; Lemonnier, T.; Latsis, T.; Turhan, A. G.; Bennaceur-Griscelli, A. Molecular investigation of adequate sources of mesenchymal stem cells for cell therapy of COVID-19-associated organ failure. Stem Cells Transl. Med. 2021, 10, 568–571.
DOI Google Scholar
[49]

Barberi, T.; Willis, L. M.; Socci, N. D.; Studer, L. Derivation of multipotent mesenchymal precursors from human embryonic stem cells. PLoS Med. 2005, 2, e161.
DOI Google Scholar
[50]

Ge, X. Y.; Li, J. L.; Yang, X. L.; Chmura, A. A.; Zhu, G. J.; Epstein, J. H.; Mazet, J. K.; Hu, B.; Zhang, W.; Peng, C. et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature 2013, 503, 535–538.
DOI Google Scholar
[51]

Leng, Z. K.; Zhu, R. J.; Hou, W.; Feng, Y. M.; Yang, Y. L.; Han, Q.; Shan, G. L.; Meng, F. Y.; Du, D. S.; Wang, S. H. et al. Transplantation of ACE2-mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis. 2020, 11, 216–228.
DOI Google Scholar
[52]

Bari, E.; Ferrarotti, I.; Saracino, L.; Perteghella, S.; Torre, M. L.; Corsico, A. G. Mesenchymal stromal cell secretome for severe COVID-19 infections: Premises for the therapeutic use. Cells 2020, 9, 924.
DOI Google Scholar
[53]

Mardpour, S.; Hassani, S. N.; Mardpour, S.; Sayahpour, F.; Vosough, M.; Ai, J.; Aghdami, N.; Hamidieh, A. A.; Baharvand, H. Extracellular vesicles derived from human embryonic stem cell-MSCs ameliorate cirrhosis in thioacetamide-induced chronic liver injury. J. Cell. Physiol. 2018, 233, 9330–9344.
DOI Google Scholar
[54]

Ohara, M.; Ohnishi, S.; Hosono, H.; Yamamoto, K.; Yuyama, K.; Nakamura, H.; Fu, Q. J.; Maehara, O.; Suda, G.; Sakamoto, N. Extracellular vesicles from amnion-derived mesenchymal stem cells ameliorate hepatic inflammation and fibrosis in rats. Stem Cells Int. 2018, 2018, 3212643.
DOI Google Scholar
[55]

Zhu, Z.; Han, C. N.; Xian, S. L.; Zhuang, F.; Ding, F.; Zhang, W.; Liu, Y. L. Placental mesenchymal stromal cells (PMSCs) and PMSC-derived extracellular vesicles (PMSC-EVs) attenuated renal fibrosis in rats with unilateral ureteral obstruction (UUO) by regulating CD4+ T cell polarization. Stem Cells Int. 2020, 2020, 2685820.
DOI Google Scholar
[56]

Zhang, S. P.; Teo, K. Y. W.; Chuah, S. J.; Lai, R. C.; Lim, S. K.; Toh, W. S. MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis. Biomaterials 2019, 200, 35–47.
DOI Google Scholar
[57]

Chen, Y. Q.; Shen, H.; Ding, Y. L.; Yu, Y.; Shao, L. B.; Shen, Z. Y. The application of umbilical cord-derived MSCs in cardiovascular diseases. J. Cell. Mol. Med. 2021, 25, 8103–8114.
DOI Google Scholar
[58]

Wang, T.; Jian, Z.; Baskys, A.; Yang, J. L.; Li, J.; Guo, H.; Hei, Y.; Xian, P. P.; He, Z. Z.; Li, Z. Y. et al. MSC-derived exosomes protect against oxidative stress-induced skin injury via adaptive regulation of the NRF2 defense system. Biomaterials 2020, 257, 120264.
DOI Google Scholar
[59]

Xian, P. P.; Hei, Y.; Wang, R.; Wang, T.; Yang, J. L.; Li, J. Y.; Di, Z. L.; Liu, Z. Q.; Baskys, A.; Liu, W. P. et al. Mesenchymal stem cell-derived exosomes as a nanotherapeutic agent for amelioration of inflammation-induced astrocyte alterations in mice. Theranostics 2019, 9, 5956–5975.
DOI Google Scholar
[60]

Long, Q. F.; Upadhya, D.; Hattiangady, B.; Kim, D. K.; An, S. Y.; Shuai, B.; Prockop, D. J.; Shetty, A. K. Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. Proc. Natl. Acad. Sci. USA 2017, 114, E3536–E3545.
DOI Google Scholar
[61]

Ding, M.; Shen, Y.; Wang, P.; Xie, Z. H.; Xu, S. L.; Zhu, Z. Y.; Wang, Y.; Lyu, Y. T.; Wang, D. W.; Xu, L. L. et al. Exosomes isolated from human umbilical cord mesenchymal stem cells alleviate neuroinflammation and reduce amyloid-beta deposition by modulating microglial activation in Alzheimer’s disease. Neurochem. Res. 2018, 43, 2165–2177.
DOI Google Scholar
[62]

Sun, G. D.; Li, G. Q.; Li, D. H.; Huang, W. J.; Zhang, R. W.; Zhang, H.; Duan, Y. Y.; Wang, B. C. hucMSC derived exosomes promote functional recovery in spinal cord injury mice via attenuating inflammation. Mater. Sci. Eng.: C 2018, 89, 194–204.
DOI Google Scholar
[63]

Liu, W.; Rong, Y. L.; Wang, J. X.; Zhou, Z.; Ge, X. H.; Ji, C. Y.; Jiang, D. D.; Gong, F. Y.; Li, L. W.; Chen, J. et al. Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization. J. Neuroinflammation 2020, 17, 47.
DOI Google Scholar
[64]

Huang, J. H.; Fu, C. H.; Xu, Y.; Yin, X. M.; Cao, Y.; Lin, F. Y. Extracellular vesicles derived from epidural fat-mesenchymal stem cells attenuate NLRP3 inflammasome activation and improve functional recovery after spinal cord injury. Neurochem. Res. 2020, 45, 760–771.
DOI Google Scholar
[65]

Jiang, D. D.; Gong, F. Y.; Ge, X. H.; Lv, C. T.; Huang, C. Y.; Feng, S.; Zhou, Z.; Rong, Y. L.; Wang, J. X.; Ji, C. et al. Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes. J. Nanobiotechnol. 2020, 18, 105.
DOI Google Scholar
[66]

Rong, Y. L.; Liu, W.; Wang, J. X.; Fan, J.; Luo, Y. J.; Li, L. W.; Kong, F. Q.; Chen, J.; Tang, P. Y.; Cai, W. H. Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy. Cell Death Dis. 2019, 10, 340.
DOI Google Scholar
[67]

Li, L. M.; Zhang, Y.; Mu, J. F.; Chen, J. C.; Zhang, C. Y.; Cao, H. C.; Gao, J. Q. Transplantation of human mesenchymal stem-cell-derived exosomes immobilized in an adhesive hydrogel for effective treatment of spinal cord injury. Nano Lett. 2020, 20, 4298–4305.
DOI Google Scholar
[68]

Haney, M. J.; Klyachko, N. L.; Zhao, Y. L.; Gupta, R.; Plotnikova, E. G.; He, Z. J.; Patel, T.; Piroyan, A.; Sokolsky, M.; Kabanov, A. V. et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J. Controll. Release 2015, 207, 18–30.
DOI Google Scholar
[69]

Mathew, B.; Ravindran, S.; Liu, X. R.; Torres, L.; Chennakesavalu, M.; Huang, C. C.; Feng, L.; Zelka, R.; Lopez, J.; Sharma, M. et al. Mesenchymal stem cell-derived extracellular vesicles and retinal ischemia-reperfusion. Biomaterials 2019, 197, 146–160.
DOI Google Scholar
[70]

Tao, H. Y.; Chen, X. N.; Cao, H. M.; Zheng, L. Y.; Li, Q.; Zhang, K. Y.; Han, Z. B.; Han, Z. C.; Guo, Z. K.; Li, Z. J. et al. Mesenchymal stem cell-derived extracellular vesicles for corneal wound repair. Stem Cells Int. 2019, 2019, 5738510.
DOI Google Scholar
[71]

Yu, C. Q.; Chen, P.; Xu, J.; Liu, Y. N.; Li, H.; Wang, L. N.; Di, G. H. hADSCs derived extracellular vesicles inhibit NLRP3 inflammasome activation and dry eye. Sci. Rep. 2020, 10, 14521.
DOI Google Scholar
[72]

Tang, Q. M.; Lu, B.; He, J.; Chen, X.; Fu, Q. L.; Han, H. J.; Luo, C. Q.; Yin, H. F.; Qin, Z. W.; Lyu, D. et al. Exosomes-loaded thermosensitive hydrogels for corneal epithelium and stroma regeneration. Biomaterials 2022, 280, 121320.
DOI Google Scholar
[73]

Du, Y. M.; Zhuansun, Y. X.; Chen, R.; Lin, L.; Lin, Y.; Li, J. G. Mesenchymal stem cell exosomes promote immunosuppression of regulatory T cells in asthma. Exp. Cell Res. 2018, 363, 114–120.
DOI Google Scholar
[74]

Jiao, Y.; Zhang, T.; Zhang, C. M.; Ji, H. Y.; Tong, X. Y.; Xia, R.; Wang, W.; Ma, Z. L.; Shi, X. Y. Exosomal miR-30d-5p of neutrophils induces M1 macrophage polarization and primes macrophage pyroptosis in sepsis-related acute lung injury. Crit. Care 2021, 25, 356.
DOI Google Scholar
[75]

Yi, X. M.; Wei, X. X.; Lv, H. J.; An, Y. L.; Li, L. J.; Lu, P. L.; Yang, Y.; Zhang, Q.; Yi, H. M.; Chen, G. H. Exosomes derived from microRNA-30b-3p-overexpressing mesenchymal stem cells protect against lipopolysaccharide-induced acute lung injury by inhibiting SAA3. Exp. Cell Res. 2019, 383, 111454.
DOI Google Scholar
[76]

Dinh, P. U. C.; Paudel, D.; Brochu, H.; Popowski, K. D.; Gracieux, M. C.; Cores, J.; Huang, K.; Hensley, M. T.; Harrell, E.; Vandergriff, A. C. et al. Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis. Nat. Commun. 2020, 11, 1064.
DOI Google Scholar
[77]

Fang, S. B.; Zhang, H. Y.; Meng, X. C.; Wang, C.; He, B. X.; Peng, Y. Q.; Xu, Z. B.; Fan, X. L.; Wu, Z. J.; Wu, Z. C. et al. Small extracellular vesicles derived from human MSCs prevent allergic airway inflammation via immunomodulation on pulmonary macrophages. Cell Death Dis. 2020, 11, 409.
DOI Google Scholar
[78]

Ma, X. Y.; Guo, S. Y.; Ruan, S. R.; Liu, Y.; Zang, J.; Yang, Y. S.; Dong, H. Q.; Li, Y.; Ren, T. B.; An, M. M. et al. HACE2-exosome-based nano-bait for concurrent SARS-CoV-2 trapping and antioxidant therapy. ACS Appl Mater Interfaces 2022, 14, 4882–4891.
DOI Google Scholar
[79]

Bruno, S.; Pasquino, C.; Herrera Sanchez, M. B.; Tapparo, M.; Figliolini, F.; Grange, C.; Chiabotto, G.; Cedrino, M.; Deregibus, M. C.; Tetta, C. et al. HLSC-derived extracellular vesicles attenuate liver fibrosis and inflammation in a murine model of non-alcoholic steatohepatitis. Mol Ther. 2020, 28, 479–489.
DOI Google Scholar
[80]

Li, X. L.; Chen, R. J.; Kemper, S.; Brigstock, D. R. Extracellular vesicles from hepatocytes are therapeutic for toxin-mediated fibrosis and gene expression in the liver. Front. Cell Dev. Biol. 2020, 7, 368.
DOI Google Scholar
[81]

Kawata, R.; Oda, S.; Koya, Y.; Kajiyama, H.; Yokoi, T. Macrophage-derived extracellular vesicles regulate concanavalin A-induced hepatitis by suppressing macrophage cytokine production. Toxicology 2020, 443, 152544.
DOI Google Scholar
[82]

Zheng, J.; Lu, T. Y.; Zhou, C. R.; Cai, J. Y.; Zhang, X. M.; Liang, J. L.; Sui, X.; Chen, X. Y.; Chen, L.; Sun, Y. et al. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells protect liver ischemia/reperfusion injury by reducing CD154 expression on CD4+ T cells via CCT2. Adv. Sci. 2020, 7, 1903746.
DOI Google Scholar
[83]

Yao, J.; Zheng, J.; Cai, J. Y.; Zeng, K. N.; Zhou, C. R.; Zhang, J. B.; Li, S. H.; Li, H.; Chen, L.; He, L. Y. et al. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response. FASEB J. 2019, 33, 1695–1710.
DOI Google Scholar
[84]

Woo, C. H.; Kim, H. K.; Jung, G. Y.; Jung, Y. J.; Lee, K. S.; Yun, Y. E.; Han, J.; Lee, J.; Kim, W. S.; Choi, J. S. et al. Small extracellular vesicles from human adipose-derived stem cells attenuate cartilage degeneration. J. Extracell. Vesicles 2020, 9, 1735249.
DOI Google Scholar
[85]

Wu, J. Y.; Kuang, L.; Chen, C.; Yang, J. J.; Zeng, W. N.; Li, T.; Chen, H.; Huang, S.; Fu, Z. L.; Li, J. M. et al. miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis. Biomaterials 2019, 206, 87–100.
DOI Google Scholar
[86]

Xu, C.; Zhai, Z. J.; Ying, H.; Lu, L.; Zhang, J.; Zeng, Y. M. Curcumin primed ADMSCs derived small extracellular vesicle exert enhanced protective effects on osteoarthritis by inhibiting oxidative stress and chondrocyte apoptosis. J. Nanobiotechnol. 2022, 20, 123.
DOI Google Scholar
[87]

Li, Y. L.; Tu, Q. Q.; Xie, D. M.; Chen, S. R.; Gao, K.; Xu, X. C.; Zhang, Z. J.; Mei, X. F. Triamcinolone acetonide-loaded nanoparticles encapsulated by CD90+ MCSs-derived microvesicles drive anti-inflammatory properties and promote cartilage regeneration after osteoarthritis. J. Nanobiotechnol. 2022, 20, 150.
DOI Google Scholar
[88]

Liu, A. L.; Wang, Q.; Zhao, Z. N.; Wu, R.; Wang, M. C.; Li, J. W.; Sun, K. Y.; Sun, Z. Y.; Lv, Z. Y.; Xu, J. et al. Nitric oxide nanomotor driving exosomes-loaded microneedles for achilles tendinopathy healing. ACS Nano 2021, 15, 13339–13350.
DOI Google Scholar
[89]

Han, C. S.; Liu, F.; Zhang, Y.; Chen, W. J.; Luo, W.; Ding, F. Z.; Lu, L.; Wu, C. J.; Li, Y. X. Human umbilical cord mesenchymal stem cell derived exosomes delivered using silk fibroin and sericin composite hydrogel promote wound healing. Front. Cardiovasc. Med. 2021, 8, 713021.
DOI Google Scholar
[90]

Yuan, M.; Liu, K.; Jiang, T.; Li, S. B.; Chen, J.; Wu, Z. H.; Li, W. Q.; Tan, R. Z.; Wei, W. Y.; Yang, X. F. et al. GelMA/PEGDA microneedles patch loaded with HUVECs-derived exosomes and Tazarotene promote diabetic wound healing. J. Nanobiotechnol. 2022, 20, 147.
DOI Google Scholar
[91]

Cho, B. S.; Kim, J. O.; Ha, D. H.; Yi, Y. W. Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis. Stem Cell Res. Ther. 2018, 9, 187.
DOI Google Scholar
[92]

Shin, K. O.; Ha, D. H.; Kim, J. O.; Crumrine, D. A.; Meyer, J. M.; Wakefield, J. S.; Lee, Y.; Kim, B.; Kim, S.; Kim, H. K. et al. Exosomes from human adipose tissue-derived mesenchymal stem cells promote epidermal barrier repair by inducing de novo synthesis of ceramides in atopic dermatitis. Cells 2020, 9, 680.
DOI Google Scholar
[93]

Zhang, B.; Lai, R. C.; Sim, W. K.; Choo, A. B. H.; Lane, E. B.; Lim, S. K. Topical application of mesenchymal stem cell exosomes alleviates the imiquimod induced psoriasis-like inflammation. Int. J. Mol. Sci. 2021, 22, 720.
DOI Google Scholar
[94]

Hu, S. Q.; Li, Z. H.; Cores, J.; Huang, K.; Su, T.; Dinh, P. U.; Cheng, K. Needle-free injection of exosomes derived from human dermal fibroblast spheroids ameliorates skin photoaging. ACS Nano 2019, 13, 11273–11282.
DOI Google Scholar
[95]

Thomi, G.; Surbek, D.; Haesler, V.; Joerger-Messerli, M.; Schoeberlein, A. Exosomes derived from umbilical cord mesenchymal stem cells reduce microglia-mediated neuroinflammation in perinatal brain injury. Stem Cell Res. Ther. 2019, 10, 105.
DOI Google Scholar
[96]

Kilpinen, L.; Impola, U.; Sankkila, L.; Ritamo, I.; Aatonen, M.; Kilpinen, S.; Tuimala, J.; Valmu, L.; Levijoki, J.; Finckenberg, P. et al. Extracellular membrane vesicles from umbilical cord blood-derived MSC protect against ischemic acute kidney injury, a feature that is lost after inflammatory conditioning. J. Extracell. Vesicles 2013, 2, 21927.
DOI Google Scholar
[97]

Nassar, W.; El-Ansary, M.; Sabry, D.; Mostafa, M. A.; Fayad, T.; Kotb, E.; Temraz, M.; Saad, A. N.; Essa, W.; Adel, H. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater. Res. 2016, 20, 21.
DOI Google Scholar
[98]

Wang, G. Y.; Yuan, J. T.; Cai, X.; Xu, Z. W.; Wang, J. Y.; Ocansey, D. K. W.; Yan, Y. M.; Qian, H.; Zhang, X.; Xu, W. R. et al. HucMSC-exosomes carrying miR-326 inhibit neddylation to relieve inflammatory bowel disease in mice. Clin. Transl. Med. 2020, 10, e113.
DOI Google Scholar
[99]

Mao, F.; Wu, Y. B.; Tang, X. D.; Kang, J. J.; Zhang, B.; Yan, Y. M.; Qian, H.; Zhang, X.; Xu, W. R. Exosomes derived from human umbilical cord mesenchymal stem cells relieve inflammatory bowel disease in mice. Biomed Res. Int. 2017, 2017, 5356760.
DOI Google Scholar
[100]

Strioga, M.; Viswanathan, S.; Darinskas, A.; Slaby, O.; Michalek, J. Same or not the same? Comparison of adipose tissue-derived versus bone marrow-derived mesenchymal stem and stromal cells. Stem Cells Dev. 2012, 21, 2724–2752.
DOI Google Scholar
[101]

Bassi, G.; Pacelli, L.; Carusone, R.; Zanoncello, J.; Krampera, M. Adipose-derived stromal cells (ASCs). Transfus. Apher. Sci. 2012, 47, 193–198.
DOI Google Scholar
[102]

Langan, S. M.; Irvine, A. D.; Weidinger, S. Atopic dermatitis. Lancet 2020, 396, 345–360.
DOI Google Scholar
[103]

Liu, J. W.; Jiang, M.; Deng, S. Q.; Lu, J. D.; Huang, H.; Zhang, Y.; Gong, P. H.; Shen, X. M.; Ruan, H. J.; Jin, M. M. et al. miR-93-5p-containing exosomes treatment attenuates acute myocardial infarction-induced myocardial damage. Mol. Ther. - Nucleic Acids 2018, 11, 103–115.
DOI Google Scholar
[104]

Eirin, A.; Zhu, X. Y.; Puranik, A. S.; Tang, H.; McGurren, K. A.; van Wijnen, A. J.; Lerman, A.; Lerman, L. O. Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation. Kidney Int. 2017, 92, 114–124.
DOI Google Scholar
[105]

Jin, Y. P.; Wang, J. Y.; Li, H. C.; Gao, S. N.; Shi, R. F.; Yang, D. J.; Wang, X. L.; Wang, X.; Zhu, L.; Wang, X. J. et al. Extracellular vesicles secreted by human adipose-derived stem cells (hASCs) improve survival rate of rats with acute liver failure by releasing lncRNA H19. EBioMedicine 2018, 34, 231–242.
DOI Google Scholar
[106]

Sobo-Vujanovic, A.; Munich, S.; Vujanovic, N. L. Dendritic-cell exosomes cross-present Toll-like receptor-ligands and activate bystander dendritic cells. Cell. Immunol. 2014, 289, 119–127.
DOI Google Scholar
[107]

Vukman, K. V.; Försönits, A.; Oszvald, Á.; Tóth, E. Á.; Buzás, E. I. Mast cell secretome: Soluble and vesicular components. Semin. Cell Dev. Biol. 2017, 67, 65–73.
DOI Google Scholar
[108]

Lee, H. D.; Kim, Y. H.; Kim, D. S. Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking. Eur. J. Immunol. 2014, 44, 1156–1169.
DOI Google Scholar
[109]

McDonald, M. K.; Tian, Y. Z.; Qureshi, R. A.; Gormley, M.; Ertel, A.; Gao, R.; Aradillas Lopez, E.; Alexander, G. M.; Sacan, A.; Fortina, P. et al. Functional significance of macrophage-derived exosomes in inflammation and pain. Pain 2014, 155, 1527–1539.
DOI Google Scholar
[110]

Buschow, S. I.; van Balkom, B. W. M.; Aalberts, M.; Heck, A. J. R.; Wauben, M.; Stoorvogel, W. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunol. Cell Biol. 2010, 88, 851–856.
DOI Google Scholar
[111]

Yu, X. S.; Huang, C. B.; Song, B.; Xiao, Y.; Fang, M. O.; Feng, J. Y.; Wang, P. X. CD4+CD25+ regulatory T cells-derived exosomes prolonged kidney allograft survival in a rat model. Cell. Immunol. 2013, 285, 62–68.
DOI Google Scholar
[112]

Zhang, H. F.; Xie, Y. F.; Li, W.; Chibbar, R.; Xiong, S. D.; Xiang, J. CD4+ T cell-released exosomes inhibit CD8+ cytotoxic T-lymphocyte responses and antitumor immunity. Cell. Mol. Immunol. 2011, 8, 23–30.
DOI Google Scholar
[113]

Marar, C.; Starich, B.; Wirtz, D. Extracellular vesicles in immunomodulation and tumor progression. Nat. Immunol. 2021, 22, 560–570.
DOI Google Scholar
[114]

Lu, J.; Wu, J.; Tian, J.; Wang, S. J. Role of T cell-derived exosomes in immunoregulation. Immunol. Res. 2018, 66, 313–322.
DOI Google Scholar
[115]

Li, M. S.; Zhao, J. H.; Cao, M. W.; Liu, R. T.; Chen, G. H.; Li, S. Y.; Xie, Y. W.; Xie, J.; Cheng, Y.; Huang, L. et al. Mast cells-derived MiR-223 destroys intestinal barrier function by inhibition of CLDN8 expression in intestinal epithelial cells. Biol. Res. 2020, 53, 12.
DOI Google Scholar
[116]

Julich, H.; Willms, A.; Lukacs-Kornek, V.; Kornek, M. Extracellular vesicle profiling and their use as potential disease specific biomarker. Front. Immunol. 2014, 5, 413.
DOI Google Scholar
[117]

Kornek, M.; Lynch, M.; Mehta, S. H.; Lai, M.; Exley, M.; Afdhal, N. H.; Schuppan, D. Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis. Gastroenterology 2012, 143, 448–458.
DOI Google Scholar
[118]

Bu, N.; Wu, H. Q.; Zhang, G. L.; Zhan, S. Q.; Zhang, R.; Fan, Q. Y.; Li, Y. L.; Zhai, Y. F.; Ren, H. W. Immature dendritic cell exosomes suppress experimental autoimmune myasthenia gravis. J. Neuroimmunol. 2015, 285, 71–75.
DOI Google Scholar
[119]

Yin, W. F.; Ouyang, S.; Li, Y.; Xiao, B.; Yang, H. Immature dendritic cell-derived exosomes: A promise subcellular vaccine for autoimmunity. Inflammation 2013, 36, 232–240.
DOI Google Scholar
[120]

Liu, H. B.; Gao, W.; Yuan, J.; Wu, C. N.; Yao, K.; Zhang, L.; Ma, L. L.; Zhu, J. B.; Zou, Y. Z.; Ge, J. B. Exosomes derived from dendritic cells improve cardiac function via activation of CD4+ T lymphocytes after myocardial infarction. J. Mol. Cell. Cardiol. 2016, 91, 123–133.
DOI Google Scholar
[121]

Aiello, S.; Rocchetta, F.; Longaretti, L.; Faravelli, S.; Todeschini, M.; Cassis, L.; Pezzuto, F.; Tomasoni, S.; Azzollini, N.; Mister, M. et al. Extracellular vesicles derived from T regulatory cells suppress T cell proliferation and prolong allograft survival. Sci. Rep. 2017, 7, 11518.
DOI Google Scholar
[122]

Song, J. P.; Huang, J.; Chen, X.; Teng, X.; Song, Z. Z.; Xing, Y.; Wang, M. Y.; Chen, K.; Wang, Z.; Yang, P. C. et al. Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart. Sci. Rep. 2016, 6, 20077.
DOI Google Scholar
[123]

Agarwal, A.; Fanelli, G.; Letizia, M.; Tung, S. L.; Boardman, D.; Lechler, R.; Lombardi, G.; Smyth, L. A. Regulatory T cell-derived exosomes: Possible therapeutic and diagnostic tools in transplantation. Front. Immunol. 2014, 5, 555.
DOI Google Scholar
[124]

Yin, X. Z.; Zeng, W. F.; Wu, B. W.; Wang, L. Y.; Wang, Z. H.; Tian, H. J.; Wang, L. Y.; Jiang, Y. H.; Clay, R.; Wei, X. L. et al. PPARα inhibition overcomes tumor-derived exosomal lipid-induced dendritic cell dysfunction. Cell Rep. 2020, 33, 108278.
DOI Google Scholar
[125]

Panwar, P.; Butler, G. S.; Jamroz, A.; Azizi, P.; Overall, C. M.; Brömme, D. Aging-associated modifications of collagen affect its degradation by matrix metalloproteinases. Matrix Biol. 2018, 65, 30–44.
DOI Google Scholar
[126]

Xia, W. Z.; Li, M. X.; Jiang, X. Y.; Huang, X.; Gu, S. C.; Ye, J. Q.; Zhu, L. X.; Hou, M.; Zan, T. Young fibroblast-derived exosomal microRNA-125b transfers beneficial effects on aged cutaneous wound healing. J. Nanobiotechnol. 2022, 20, 144.
DOI Google Scholar
[127]

Shi, A.; Li, J. L.; Qiu, X. Y.; Sabbah, M.; Boroumand, S.; Huang, T. C. T.; Zhao, C. F.; Terzic, A.; Behfar, A.; Moran, S. L. TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo. Theranostics 2021, 11, 6616–6631.
DOI Google Scholar
[128]

Xu, L. Y.; Botchway, B. O. A.; Zhang, S.; Zhou, J. Y.; Liu, X. H. Inhibition of NF-κB signaling pathway by resveratrol improves spinal cord injury. Front. Neurosci. 2018, 12, 690.
DOI Google Scholar
[129]

Melnik, B. C.; Schmitz, G. Milk’s role as an epigenetic regulator in health and disease. Diseases 2017, 5, 12.
DOI Google Scholar
[130]

Reinhardt, T. A.; Lippolis, J. D.; Nonnecke, B. J.; Sacco, R. E. Bovine milk exosome proteome. J. Proteomics 2012, 75, 1486–1492.
DOI Google Scholar
[131]

Samuel, M.; Chisanga, D.; Liem, M.; Keerthikumar, S.; Anand, S.; Ang, C. S.; Adda, C. G.; Versteegen, E.; Jois, M.; Mathivanan, S. Bovine milk-derived exosomes from colostrum are enriched with proteins implicated in immune response and growth. Sci. Rep. 2017, 7, 5933.
DOI Google Scholar
[132]

Zhou, Q.; Li, M. Z.; Wang, X. Y.; Li, Q. Z.; Wang, T.; Zhu, Q.; Zhou, X. C.; Wang, X.; Gao, X. L.; Li, X. W. Immune-related microRNAs are abundant in breast milk exosomes. Int. J. Biol. Sci. 2012, 8, 118–123.
DOI Google Scholar
[133]

Zhong, J.; Xia, B. Z.; Shan, S. B.; Zheng, A. P.; Zhang, S. W.; Chen, J. G.; Liang, X. J. High-quality milk exosomes as oral drug delivery system. Biomaterials 2021, 277, 121126.
DOI Google Scholar
[134]

Reif, S.; Elbaum-Shiff, Y.; Koroukhov, N.; Shilo, I.; Musseri, M.; Golan-Gerstl, R. Cow and human milk-derived exosomes ameliorate colitis in DSS murine model. Nutrients 2020, 12, 2589.
DOI Google Scholar
[135]

Sanwlani, R.; Fonseka, P.; Chitti, S. V.; Mathivanan, S. Milk-derived extracellular vesicles in inter-organism, cross-species communication and drug delivery. Proteomes 2020, 8, 11.
DOI Google Scholar
[136]

van Baarlen, P.; Wells, J. M.; Kleerebezem, M. Regulation of intestinal homeostasis and immunity with probiotic lactobacilli. Trends Immunol. 2013, 34, 208–215.
DOI Google Scholar
[137]

Kim, M. H.; Choi, S. J.; Choi, H. I.; Choi, J. P.; Park, H. K.; Kim, E. K.; Kim, M. J.; Moon, B. S.; Min, T. K.; Rho, M. et al. Lactobacillus plantarum-derived extracellular vesicles protect atopic dermatitis induced by staphylococcus aureus-derived extracellular vesicles. Allergy Asthma Immunol. Res. 2018, 10, 516–532.
DOI Google Scholar
[138]

Kim, W.; Lee, E. J.; Bae, I. H.; Myoung, K.; Kim, S. T.; Park, P. J.; Lee, K. H.; Pham, A. V. Q.; Ko, J.; Oh, S. H. et al. Lactobacillus plantarum-derived extracellular vesicles induce anti-inflammatory M2 macrophage polarization in vitro. J. Extracell. Vesicles 2020, 9, 1793514.
DOI Google Scholar
[139]

Zu, M. H.; Xie, D. C.; Canup, B. S. B.; Chen, N. X.; Wang, Y. J.; Sun, R. X.; Zhang, Z.; Fu, Y. M.; Dai, F. Y.; Xiao, B. “Green” nanotherapeutics from tea leaves for orally targeted prevention and alleviation of colon diseases. Biomaterials 2021, 279, 121178.
DOI Google Scholar
[140]

Chen, X. Y.; Liu, B. L.; Li, X. Z.; An, T. T.; Zhou, Y.; Li, G.; Wu-Smart, J.; Alvarez, S.; Naldrett, M. J.; Eudy, J. et al. Identification of anti-inflammatory vesicle-like nanoparticles in honey. J. Extracell. Vesicles 2021, 10, e12069.
DOI Google Scholar
[141]

Kalluri, R.; LeBleu Valerie, S. The biology, function, and biomedical applications of exosomes. Science 2020, 367, eaau6977.
DOI Google Scholar
[142]

Zhang, Y.; Liu, Y. F.; Liu, H. Y.; Tang, W. H. Exosomes: Biogenesis, biologic function and clinical potential. Cell Biosci. 2019, 9, 19.
DOI Google Scholar
[143]

Veerman, R. E.; Güçlüler Akpinar, G.; Eldh, M.; Gabrielsson, S. Immune cell-derived extracellular vesicles-functions and therapeutic applications. Trends Mol. Med. 2019, 25, 382–394.
DOI Google Scholar
[144]

de Abreu, R. C.; Fernandes, H.; da Costa Martins, P. A.; Sahoo, S.; Emanueli, C.; Ferreira, L. Native and bioengineered extracellular vesicles for cardiovascular therapeutics. Nat. Rev. Cardiol. 2020, 17, 685–697.
DOI Google Scholar
[145]

Agrawal, A. K.; Aqil, F.; Jeyabalan, J.; Spencer, W. A.; Beck, J.; Gachuki, B. W.; Alhakeem, S. S.; Oben, K.; Munagala, R.; Bondada, S. et al. Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine 2017, 13, 1627–1636.
DOI Google Scholar
[146]

Luan, X.; Sansanaphongpricha, K.; Myers, I.; Chen, H. W.; Yuan, H. B.; Sun, D. X. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol. Sin. 2017, 38, 754–763.
DOI Google Scholar
[147]

Li, Y. J.; Wu, J. Y.; Liu, J. H.; Xu, W. J.; Qiu, X. H.; Huang, S.; Hu, X. B.; Xiang, D. X. Artificial exosomes for translational nanomedicine. J. Nanobiotechnol. 2021, 19, 242.
DOI Google Scholar
[148]

Sun, H.; Zhang, T. Y.; Gao, J. Q. Extracellular vesicles derived from mesenchymal stem cells: A potential biodrug for acute respiratory distress syndrome treatment. BioDrugs 2022, 36, 701–715.
DOI Google Scholar
[149]

Li, X. Y.; Wang, Y.; Shi, L. Y.; Li, B. X.; Li, J.; Wei, Z. H.; Lv, H. Y.; Wu, L. Y.; Zhang, H.; Yang, B. et al. Magnetic targeting enhances the cutaneous wound healing effects of human mesenchymal stem cell-derived iron oxide exosomes. J. Nanobiotechnol. 2020, 18, 113.
DOI Google Scholar
[150]

Yuan, D. F.; Zhao, Y. L.; Banks, W. A.; Bullock, K. M.; Haney, M.; Batrakova, E.; Kabanov, A. V. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials 2017, 142, 1–12.
DOI Google Scholar
[151]

Herrmann, I. K.; Wood, M. J. A.; Fuhrmann, G. Extracellular vesicles as a next-generation drug delivery platform. Nat. Nanotechnol. 2021, 16, 748–759.
DOI Google Scholar
[152]

Kim, M. S.; Haney, M. J.; Zhao, Y. L.; Yuan, D. F.; Deygen, I.; Klyachko, N. L.; Kabanov, A. V.; Batrakova, E. V. Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: In vitro and in vivo evaluations. Nanomedicine 2018, 14, 195–204.
DOI Google Scholar
[153]

Kim, M. S.; Haney, M. J.; Zhao, Y. L.; Mahajan, V.; Deygen, I.; Klyachko, N. L.; Inskoe, E.; Piroyan, A.; Sokolsky, M.; Okolie, O. et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine 2016, 12, 655–664.
DOI Google Scholar
[154]

Wang, X. J.; Li, H. C.; Liu, X. P.; Tian, Y.; Guo, H. S.; Jiang, T.; Luo, Z. M.; Jin, K.; Kuai, X. P.; Liu, Y. et al. Enhanced photothermal therapy of biomimetic polypyrrole nanoparticles through improving blood flow perfusion. Biomaterials 2017, 143, 130–141.
DOI Google Scholar
[155]

Li, R. X.; He, Y. W.; Zhu, Y.; Jiang, L. X.; Zhang, S. Y.; Qin, J.; Wu, Q.; Dai, W. T.; Shen, S.; Pang, Z. Q. et al. Route to rheumatoid arthritis by macrophage-derived microvesicle-coated nanoparticles. Nano Lett. 2019, 19, 124–134.
DOI Google Scholar
[156]

Fuhrmann, G.; Serio, A.; Mazo, M.; Nair, R.; Stevens, M. M. Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. J. Controll. Release 2015, 205, 35–44.
DOI Google Scholar
[157]

Liang, G. F.; Zhu, Y. L.; Ali, D. J.; Tian, T.; Xu, H. T.; Si, K.; Sun, B.; Chen, B. A.; Xiao, Z. D. Engineered exosomes for targeted co-delivery of miR-21 inhibitor and chemotherapeutics to reverse drug resistance in colon cancer. J. Nanobiotechnol. 2020, 18, 10.
DOI Google Scholar
[158]

Alvarez-Erviti, L.; Seow, Y.; Yin, H. F.; Betts, C.; Lakhal, S.; Wood, M. J. A. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 2011, 29, 341–345.
DOI Google Scholar
[159]

Jin, Y.; Chen, K. Y.; Wang, Z. Y.; Wang, Y.; Liu, J. Z.; Lin, L.; Shao, Y.; Gao, L. H.; Yin, H. H.; Cui, C. et al. DNA in serum extracellular vesicles is stable under different storage conditions. BMC Cancer 2016, 16, 753.
DOI Google Scholar
[160]

Liu, Y.; Wang, X. J.; Ouyang, B. S.; Liu, X. P.; Du, Y.; Cai, X. Z.; Guo, H. S.; Pang, Z. Q.; Yang, W. L.; Shen, S. Erythrocyte-platelet hybrid membranes coating polypyrrol nanoparticles for enhanced delivery and photothermal therapy. J. Mater. Chem. B 2018, 6, 7033–7041.
DOI Google Scholar
[161]

Hu, C. M. J.; Zhang, L.; Aryal, S.; Cheung, C.; Fang, R. H.; Zhang, L. F. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc. Natl. Acad. Sci. USA 2011, 108, 10980–10985.
DOI Google Scholar
[162]

Zhu, Q. F.; Heon, M.; Zhao, Z.; He, M. Microfluidic engineering of exosomes: Editing cellular messages for precision therapeutics. Lab Chip 2018, 18, 1690–1703.
DOI Google Scholar
[163]
Oliver, C.; Jamur, M. C. Overview of antibodies for immunochemistry. In Immunocytochemical Methods and Protocols. Oliver, C.; Jamur, M. , Eds.; Humana Press: USA, 2010; pp 3–9.
[164]

Fuhrmann, G.; Chandrawati, R.; Parmar, P. A.; Keane, T. J.; Maynard, S. A.; Bertazzo, S.; Stevens, M. M. Engineering extracellular vesicles with the tools of enzyme prodrug therapy. Adv. Mater. 2018, 30, 1706616.
DOI Google Scholar
[165]

Kim, H.; Kang, J. Y.; Mun, D.; Yun, N. R.; Joung, B. Calcium chloride enhances the delivery of exosomes. PLoS One 2019, 14, e0220036.
DOI Google Scholar
[166]

Fan, L.; Liu, C.; Chen, X. X.; Zheng, L.; Zou, Y.; Wen, H. Q.; Guan, P. F.; Lu, F.; Luo, Y. A.; Tan, G. X. et al. Exosomes-loaded electroconductive hydrogel synergistically promotes tissue repair after spinal cord injury via immunoregulation and enhancement of myelinated axon growth. Adv. Sci. 2022, 9, 2105586.
DOI Google Scholar
[167]

Rzhevskiy, A. S.; Singh, T. R. R.; Donnelly, R. F.; Anissimov, Y. G. Microneedles as the technique of drug delivery enhancement in diverse organs and tissues. J. Controll. Release 2018, 270, 184–202.
DOI Google Scholar
[168]

Liang, Y. J.; Duan, L.; Lu, J. P.; Xia, J. Engineering exosomes for targeted drug delivery. Theranostics 2021, 11, 3183–3195.
DOI Google Scholar
[169]

Ingato, D.; Lee, J. U.; Sim, S. J.; Kwon, Y. J. Good things come in small packages: Overcoming challenges to harness extracellular vesicles for therapeutic delivery. J. Controll. Release 2016, 241, 174–185.
DOI Google Scholar
[170]

Wu, C. H.; Xu, Q.; Wang, H. Y.; Tu, B.; Zeng, J. X.; Zhao, P. F.; Shi, M. J.; Qiu, H.; Huang, Y. Z. Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles. Acta Pharm. Sin. B 2022, 12, 1523–1533.
DOI Google Scholar
[171]

Liang, Y. J.; Xu, X.; Li, X. F.; Xiong, J. Y.; Li, B. Q.; Duan, L.; Wang, D. P.; Xia, J. Chondrocyte-targeted MicroRNA delivery by engineered exosomes toward a cell-free osteoarthritis therapy. ACS Appl. Mater. Interfaces 2020, 12, 36938–36947.
DOI Google Scholar
[172]

Wei, Z. L.; Chen, Z. Y.; Zhao, Y. C.; Fan, F.; Xiong, W. D.; Song, S.; Yin, Y.; Hu, J. J.; Yang, K.; Yang, L. B. et al. Mononuclear phagocyte system blockade using extracellular vesicles modified with CD47 on membrane surface for myocardial infarction reperfusion injury treatment. Biomaterials 2021, 275, 121000.
DOI Google Scholar
[173]

Lin, Z.; Xiong, Y.; Meng, W. L.; Hu, Y. Q.; Chen, L. L.; Chen, L.; Xue, H.; Panayi, A. C.; Zhou, W.; Sun, Y. et al. Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant. Bioact. Mater. 2022, 13, 300–311.
DOI Google Scholar
[174]

You, D. G.; Lim, G. T.; Kwon, S.; Um, W.; Oh, B. H.; Song, S. H.; Lee, J.; Jo, D. G.; Cho, Y. W.; Park, J. H. Metabolically engineered stem cell-derived exosomes to regulate macrophage heterogeneity in rheumatoid arthritis. Sci. Adv. 2021, 7, eabe0083.
DOI Google Scholar
[175]

Choi, H.; Kim, Y.; Mirzaaghasi, A.; Heo, J.; Kim, Y. N.; Shin, J. H.; Kim, S.; Kim, N. H.; Cho, E. S.; In Yook, J. et al. Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality. Sci. Adv. 2020, 6, eaaz6980.
DOI Google Scholar
[176]

Raposo, G.; Stoorvogel, W. Extracellular vesicles: Exosomes, microvesicles, and friends. J. Cell Biol. 2013, 200, 373–383.
DOI Google Scholar
Publication history
Copyright
Acknowledgements

Publication history

Received: 15 September 2022
Revised: 28 October 2022
Accepted: 31 October 2022
Published: 27 December 2022
Issue date: May 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was financially supported through grants from the National Natural Science Foundation of China (Nos. 51773154, 31771090, 31971323, and 81871315), Shanghai Science and Technology Innovation (No. 18JC1414500), and Young Hundred-Talent Program of Tongji University.

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