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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Progress of Mesenchymal Stem Cell-Derived Exosomes in Tissue Repair

Author(s): Guifang Zhao, Yiwen Ge, Chenyingnan Zhang, Leyi Zhang, Junjie Xu*, Ling Qi* and Wenliang Li

Volume 26 , Issue 17 , 2020

Page: [2022 - 2037] Pages: 16

DOI: 10.2174/1381612826666200420144805

Price: $65


Mesenchymal stem cells (MSCs) are a kind of adult stem cells with self-replication and multidirectional differentiation, which can differentiate into tissue-specific cells under physiological conditions, maintaining tissue self-renewal and physiological functions. They play a role in the pathological condition by lateral differentiation into tissue-specific cells, replacing damaged tissue cells by playing the role of a regenerative medicine , or repairing damaged tissues through angiogenesis, thereby, regulating immune responses, inflammatory responses, and inhibiting apoptosis. It has become an important seed cell for tissue repair and organ reconstruction, and cell therapy based on MSCs has been widely used clinically. The study found that the probability of stem cells migrating to the damaged area after transplantation or differentiating into damaged cells is very low, so the researchers believe the leading role of stem cell transplantation for tissue repair is paracrine secretion, secreting growth factors, cytokines or other components. Exosomes are biologically active small vesicles secreted by MSCs. Recent studies have shown that they can transfer functional proteins, RNA, microRNAs, and lncRNAs between cells, and greatly reduce the immune response. Under the premise of promoting proliferation and inhibition of apoptosis, they play a repair role in tissue damage, which is caused by a variety of diseases. In this paper, the biological characteristics of exosomes (MSCs-exosomes) derived from mesenchymal stem cells, intercellular transport mechanisms, and their research progress in the field of stem cell therapy are reviewed.

Keywords: Mesenchymal stem cells-exosomes, tissue repair, microRNAs, lncRNAs, angiogenesis, RNA.

Almalki SG, Agrawal DK. Effects of matrix metalloproteinases on the fate of mesenchymal stem cells. Stem Cell Res Ther 2016; 7(1): 129.
[] [PMID: 27612636]
Spees JL, Lee RH, Gregory CA. Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res Ther 2016; 7(1): 125.
[] [PMID: 27581859]
van Koppen A, Joles JA, van Balkom BW, et al. Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease. PLoS One 2012; 7(6) e38746
[] [PMID: 22723882]
Cheng K, Rai P, Plagov A, et al. Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms. Exp Mol Pathol 2013; 94(3): 466-73.
[] [PMID: 23534987]
Kourembanas S. Exosomes: vehicles of intercellular signaling, biomarkers, and vectors of cell therapy. Annu Rev of Physiol 2015; 77: 13-27.
Liang X, Ding Y, Zhang Y, Tse HF, Lian Q. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant 2014; 23(9): 1045-59.
[] [PMID: 23676629]
Song M, Heo J, Chun JY, et al. The paracrine effects of mesenchymal stem cells stimulate the regeneration capacity of endogenous stem cells in the repair of a bladder-outlet-obstruction-induced overactive bladder. Stem Cells Dev 2014; 23(6): 654-63.
[] [PMID: 24192209]
Tan CY, Lai RC, Wong W, Dan YY, Lim SK, Ho HK. Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther 2014; 5(3): 76.
[] [PMID: 24915963]
Asghar S, Litherland GJ, Lockhart JC, Goodyear CS, Crilly A. Exosomes in intercellular communication and implications for osteoarthritis. Rheumatology 2019; 59(1)
[] [PMID: 31628481]
Bai J, Xie X, Lei Y, An G, He L, Chen R. Consideration of dual characters of exosomes in the tumour immune response. Cell Biol Int 2014; 38(4): 538-45.
[] [PMID: 24523154]
Park S, Ahn ES, Kim Y. Neuroblastoma SH-SY5Y cell-derived exosomes stimulate dendrite-like outgrowths and modify the differentiation of A375 melanoma cells. Cell Biol Int 2015; 39(4): 379-87.
[] [PMID: 25484139]
Zhao Y, Sun X, Cao W, et al. Exosomes derived from human umbilical cord mesenchymal stem cells relieve acute myocardial ischemic injury. Stem Cells Inter 2015. 761643
Zhu G, Pei L, Lin F, et al. Exosomes from human-bone-marrow-derived mesenchymal stem cells protect against renal ischemia/reperfusion injury via transferring miR-199a-3p. J Cell Physiol 2019; 234(12): 23736-49.
[] [PMID: 31180587]
Xu JF, Yang GH, Pan XH, et al. Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. PLoS One 2014; 9(12) e114627
[] [PMID: 25503309]
Zhang Y, Chopp M, Zhang ZG, et al. Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2D and 3D conditions improves functional recovery in rats after traumatic brain injury. Neurochem Int 2017; 111: 69-81.
Fang S, Xu C, Zhang Y, et al. Umbilical cord-derived mesenchymal stem cell-derived exosomal micrornas suppress myofibroblast differentiation by inhibiting the transforming growth factor-beta/smad2 pathway during wound healing. Stem Cells Transl Med 2016; 5(10): 1425-39.
[] [PMID: 27388239]
Katsuda T, Kosaka N, Takeshita F, Ochiya T. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Proteomics 2013; 13(10-11): 1637-53.
[] [PMID: 23335344]
Kalimuthu S, Gangadaran P, Li XJ, et al. In Vivo therapeutic potential of mesenchymal stem cell-derived extracellular vesicles with optical imaging reporter in tumor mice model. Sci Rep 2016; 6: 30418.
Park KS, Bandeira E, Shelke GV, Lässer C, Lötvall J. Enhancement of therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Stem Cell Res Ther 2019; 10(1): 288.
[] [PMID: 31547882]
Xu S, Liu C, Ji HL. Concise review: Therapeutic potential of the mesenchymal stem cell derived secretome and extracellular vesicles for radiation-induced lung injury: Progress and hypotheses. Stem Cells Transl Med 2019; 8(4): 344-54.
[] [PMID: 30618085]
Nomura Y, Fukui C, Morishita Y, Haishima Y. A biological study establishing the endotoxin limit for in vitro proliferation of human mesenchymal stem cells. Regen Ther 2017; 7: 45-51.
Boeri L, Albani D, Raimondi MT, Jacchetti E. Mechanical regulation of nucleocytoplasmic translocation in mesenchymal stem cells: characterization and methods for investigation. Biophys Rev 2019; 11(5): 817-31.
[] [PMID: 31628607]
Mathot F, Rbia N, Thaler R, Bishop AT, Van Wijnen AJ, Shin AY. Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed nerve allograft. Gene 2020; 724 144151
[] [PMID: 31626959]
Gao Y, Zhao G, Li D, Chen X, Pang J, Ke J. Isolation and multiple differentiation potential assessment of human gingival mesenchymal stem cells. Int J Mol Sci 2014; 15(11): 20982-96.
[] [PMID: 25405732]
Guo J, Zhao Y, Fei C, et al. Dicer1 downregulation by multiple myeloma cells promotes the senescence and tumor-supporting capacity and decreases the differentiation potential of mesenchymal stem cells. Cell Death Dis 2018; 9(5): 512.
[] [PMID: 29724992]
Saparov A, Ogay V, Nurgozhin T, Jumabay M, Chen WC. Preconditioning of human mesenchymal stem cells to enhance their regulation of the immune response. Stem Cells Int 2016; 2016 3924858
Rui K, Lin X, Tian J, et al. Ecto-mesenchymal stem cells: a new player for immune regulation and cell therapy. Cell Mol Immunol 2018; 15(1): 82-4.
[] [PMID: 28782759]
Shen Y, Xue C, Li X, et al. Effects of gastric cancer cell-derived exosomes on the immune regulation of mesenchymal stem cells by the nf-kb signaling pathway. Stem Cells Dev 2019; 28(7): 464-76.
[] [PMID: 30717632]
Tamatani T, Takamaru N, Ohe G, Akita K, Nakagawa T, Miyamoto Y. Expression of CD44, CD44v9, ABCG2, CD24, Bmi-1 and ALDH1 in stage I and II oral squamous cell carcinoma and their association with clinicopathological factors. Oncol Lett 2018; 16(1): 1133-40.
[] [PMID: 29963189]
Pitrone M, Pizzolanti G, Coppola A, et al. Knockdown of nanog reduces cell proliferation and induces g0/g1 cell cycle arrest in human adipose stem cells. Int J Mol Sci 2019; 20(10) E2580
[] [PMID: 31130693]
Mohamed IA, El-Badri N, Zaher A. Wnt Signaling: The double-edged sword diminishing the potential of stem cell therapy in congenital heart disease. Life Sci 2019; 239 116937
[] [PMID: 31629761]
Aryan A, Bayat M, Bonakdar S, et al. Human bone marrow mesenchymal stem cell conditioned medium promotes wound healing in deep second-degree burns in male rats. Cells Tissues Organs 2018; 206(6): 317-29.
[] [PMID: 31340210]
Kocherova I, Bryja A, Mozdziak P, et al. Human umbilical vein endothelial cells (huvecs) co-culture with osteogenic cells: From molecular communication to engineering prevascularised bone grafts. J Clin Med 2019; 8(10) E1602
[] [PMID: 31623330]
Shah S, Lee H, Park YH, et al. Three-dimensional angiogenesis assay system using co-culture spheroids formed by endothelial colony forming cells and mesenchymal stem cells. J Vis Exp 2019; (151): 151.
[] [PMID: 31609345]
Li S, Zheng X, Li H, et al. Mesenchymal stem cells ameliorate hepatic ischemia/reperfusion injury via inhibition of neutrophil recruitment. J Immunol Res 2018; 2018 7283703
Kim DY, Kim JH, Lee JC, et al. Zinc oxide nanoparticles exhibit both cyclooxygenase- and lipoxygenase-mediated apoptosis in human bone marrow-derived mesenchymal stem cells. Toxicol Res 2019; 35(1): 83-91.
[] [PMID: 30766660]
DA Costa Gonçalves F, Serafini MA, Mello HF, et al. F DACG. Bioactive factors secreted from mesenchymal stromal cells protect the intestines from experimental colitis in a three-dimensional culture. Cytotherapy 2018; 20(12): 1459-71.
[] [PMID: 30523788]
Porzionato A, Stocco E, Barbon S, Grandi F, Macchi V, De Caro R. Tissue-engineered grafts from human decellularized extracellular matrices: A systematic review and future perspectives. Int J Mol Sci 2018; 19(12) E4117
[] [PMID: 30567407]
Kim CH, Lim CY, Lee JH, Kim KC, Ahn JY, Lee EJ. Human embryonic stem cells-derived mesenchymal stem cells reduce the symptom of psoriasis in imiquimod-induced skin model. Tissue Eng Regen Med 2018; 16(1): 93-102.
[] [PMID: 30815354]
Huang R, Qin C, Wang J, et al. Differential effects of extracellular vesicles from aging and young mesenchymal stem cells in acute lung injury. Aging (Albany NY) 2019; 11(18): 7996-8014.
[] [PMID: 31575829]
Mitxitorena I, Infante A, Gener B, Rodríguez CI. Suitability and limitations of mesenchymal stem cells to elucidate human bone illness. World J Stem Cells 2019; 11(9): 578-93.
[] [PMID: 31616536]
Rathinavelu S, Guidry-Elizondo C, Banu J. Molecular modulation of osteoblasts and osteoclasts in type 2 diabetes. J Diabetes Res 2018; 2018 6354787
Villa NY, McFadden G. Virotherapy as potential adjunct therapy for graft-vs-host disease. Curr Pathobiol Rep 2018; 6(4): 247-63.
[] [PMID: 30595970]
Grau-Vorster M, Laitinen A, Nystedt J, Vives J. HLA-DR expression in clinical-grade bone marrow-derived multipotent mesenchymal stromal cells: a two-site study. Stem Cell Res Ther 2019; 10(1): 164.
[] [PMID: 31196185]
Monteiro BS, Santos BSD, Almeida BL, et al. Adipose tissue derived mesenchymal stem cell transplantation in the treatment of ischemia/reperfusion induced acute kidney injury in rats. Application route and therapeutic window1. Acta Cir Bras 2018; 33(11): 1016-26.
[] [PMID: 30517328]
Shojafar E, Soleimani Mehranjani M, Shariatzadeh SMA. Adipose-derived mesenchymal stromal cell transplantation at the graft site improves the structure and function of autografted mice ovaries: a stereological and biochemical analysis. Cytotherapy 2018; 20(11): 1324-36.
[] [PMID: 30360962]
Te Winkel J, John QE, Hosfield BD, et al. Mesenchymal stem cells promote mesenteric vasodilation through hydrogen sulfide and endothelial nitric oxide. Am J Physiol Gastrointest Liver Physiol 2019; 317(4): G441-6.
[] [PMID: 31343254]
Grange C, Skovronova R, Marabese F, Bussolati B. Stem cell-derived extracellular vesicles and kidney regeneration. Cells 2019; 8(10) E1240
[] [PMID: 31614642]
Zhao Y, Tao M, Wei M, Du S, Wang H, Wang X. Mesenchymal stem cells derived exosomal miR-323-3p promotes proliferation and inhibits apoptosis of cumulus cells in polycystic ovary syndrome (PCOS). Artif Cells Nanomed Biotechnol 2019; 47(1): 3804-13.
[] [PMID: 31549864]
Khan MA, Alanazi F, Ahmed HA, et al. iPSC-derived MSC therapy induces immune tolerance and supports long-term graft survival in mouse orthotopic tracheal transplants. Stem Cell Res Ther 2019; 10(1): 290.
[] [PMID: 31547869]
Kim K, Bou-Ghannam S, Thorp H, Grainger DW, Okano T. Human mesenchymal stem cell sheets in xeno-free media for possible allogenic applications. Sci Rep 2019; 9(1): 14415.
[] [PMID: 31595012]
Im GB, Kim YH, Kim YJ, et al. Enhancing the wound healing effect of conditioned medium collected from mesenchymal stem cells with high passage number using bioreducible nanoparticles. Int J Mol Sci 2019; 20(19) E4835
[] [PMID: 31569434]
Demirel BD, Bıçakcı Ü, Rızalar R, Alpaslan Pınarlı F, Aydın O. Histopathological effects of mesenchymal stem cells in rats with bladder and posterior urethral injuries. Turk J Med Sci 2017; 47(6): 1912-9.
[] [PMID: 29306257]
Anger F, Camara M, Ellinger E, et al. Human mesenchymal stromal cell-derived extracellular vesicles improve liver regeneration after ischemia reperfusion injury in mice. Stem Cells Dev 2019; 28(21): 1451-62.
[] [PMID: 31495270]
Paiboon N, Kamprom W, Manochantr S, et al. Gestational tissue-derived human mesenchymal stem cells use distinct combinations of bioactive molecules to suppress the proliferation of human hepatoblastoma and colorectal cancer cells. Stem Cells Int 2019; 2019 9748795
Huang P, Tian X, Li Q, Yang Y. New strategies for improving stem cell therapy in ischemic heart disease. Heart Fail Rev 2016; 21(6): 737-52.
[] [PMID: 27459850]
Garrido V, Mendoza-Torres E, Riquelme JA, et al. Novel therapies targeting cardioprotection and regeneration. Curr Pharm Des 2017; 23(18): 2592-615.
[] [PMID: 28079007]
Pourakbari R, Khodadadi M, Aghebati-Maleki A, Aghebati-Maleki L, Yousefi M. The potential of exosomes in the therapy of the cartilage and bone complications; emphasis on osteoarthritis. Life Sci 2019; 236 116861
Klymiuk MC, Balz N, Elashry MI, Heimann M, Wenisch S, Arnhold S. Exosomes isolation and identification from equine mesenchymal stem cells. BMC Vet Res 2019; 15(1): 42.
[] [PMID: 30691449]
He C, Zheng S, Luo Y, Wang B. Exosome theranostics: Biology and translational medicine. Theranostics 2018; 8(1): 237-55.
[] [PMID: 29290805]
Jiao YJ, Jin DD, Jiang F, et al. Characterization and proteomic profiling of pancreatic cancer-derived serum exosomes. J Cell Biochem 2019; 120(1): 988-99.
[] [PMID: 30160795]
El-Tookhy OS, Shamaa AA, Shehab GG, Abdallah AN, Azzam OM. Histological evaluation of experimentally induced critical size defect skin wounds using exosomal solution of mesenchymal stem cells derived microvesicles. Int J Stem Cells 2017; 10(2): 144-53.
[] [PMID: 29084422]
Manuel GE, Johnson T, Liu D. Therapeutic angiogenesis of exosomes for ischemic stroke. Int J Physiol Pathophysiol Pharmacol 2017; 9(6): 188-91.
[PMID: 29348795]
Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci 2018; 75(2): 193-208.
[] [PMID: 28733901]
Safwat A, Sabry D, Ragiae A, Amer E, Mahmoud RH, Shamardan RM. Adipose mesenchymal stem cells-derived exosomes attenuate retina degeneration of streptozotocin-induced diabetes in rabbits. J Circ Biomark 2018; 7 1849454418807827
Zhao MZ, Li YP, Geng XR, et al. Expression level of micrna-126 in serum exosomes of allergic asthma patients and lung tissues of asthmatic mice. Curr Drug Metab 2019; 20(10): 799-803.
Fan L, Li R, Pan J, Ding Z, Lin J. Endocytosis and its regulation in plants. Trends Plant Sci 2015; 20(6): 388-97.
[] [PMID: 25914086]
Mulcahy LA, Pink RC, Carter DR. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles 2014; 3: 3.
[] [PMID: 25143819]
Silva BM, Prados-Rosales R, Espadas-Moreno J, et al. Characterization of Alternaria infectoria extracellular vesicles. Med Mycol 2014; 52(2): 202-10.
[] [PMID: 24576997]
Pilkis SJ, El-Maghrabi MR, Pilkis J, Claus T. Inhibition of fructose-1,6-bisphosphatase by fructose 2,6-bisphosphate. J Biol Chem 1981; 256(8): 3619-22.
[PMID: 6260770]
Yin J, Xu K, Zhang J, Kumar A, Yu FS. Wound-induced ATP release and EGF receptor activation in epithelial cells. J Cell Sci 2007; 120(Pt 5): 815-25.
[] [PMID: 17284517]
Arslan F, Lai RC, Smeets MB, et al. Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res (Amst) 2013; 10(3): 301-12.
[] [PMID: 23399448]
Davies A, Simmons DL, Hale G, et al. CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells. J Exp Med 1989; 170(3): 637-54.
[] [PMID: 2475570]
Upadhya D, Shetty AK. Extracellular vesicles as therapeutics for brain injury and disease. Curr Pharm Des 2019; 25(33): 3500-5.
[] [PMID: 31612823]
Cumba Garcia LM, Peterson TE, Cepeda MA, Johnson AJ, Parney IF. Isolation and analysis of plasma-derived exosomes in patients with glioma. Front Oncol 2019; 9: 651.
Huang S, Wang L, Bruce TF, Marcus RK. Isolation and quantification of human urinary exosomes by hydrophobic interaction chromatography on a polyester capillary-channeled polymer fiber stationary phase. Anal Bioanal Chem 2019; 411(25): 6591-601.
[] [PMID: 31372698]
Sjoqvist S, Imafuku A, Ghupta D, Andaloussi SEl. Isolation and characterization of extracellular vesicles from keratinocyte cultures. Methods Mol Biol 2020; 2109: 35-44.
Konala VB, Mamidi MK, Bhonde R, Das AK, Pochampally R, Pal R. The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration. Cytotherapy 2016; 18(1): 13-24.
[] [PMID: 26631828]
Ban JJ, Lee M, Im W, Kim M. Low pH increases the yield of exosome isolation. Biochem Biophys Res Commun 2015; 461(1): 76-9.
[] [PMID: 25849885]
Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 2009; 9(8): 581-93.
[] [PMID: 19498381]
Sahoo S, Klychko E, Thorne T, et al. Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity. Circ Res 2011; 109(7): 724-8.
[] [PMID: 21835908]
Mathiyalagan P, Liang Y, Kim D, et al. Angiogenic mechanisms of human cd34(+) stem cell exosomes in the repair of ischemic hindlimb. Circ Res 2017; 120(9): 1466-76.
[] [PMID: 28298297]
Coumans FA, van der Pol E, Boing AN, et al. Reproducible extracellular vesicle size and concentration determination with tunable resistive pulse sensing. J Extracellular Vesicles 2014; 3: 25922.
Lobb RJ, Becker M, Wen SW, et al. Optimized exosome isolation protocol for cell culture supernatant and human plasma. J Extracellular Vesicles 2015; 4: 27031.
van der Pol E, van Gemert MJ, Sturk A, Nieuwland R, van Leeuwen TG. Single vs. swarm detection of microparticles and exosomes by flow cytometry. J Thromb Haemost 2012; 10(5): 919-30.
[] [PMID: 22394434]
Lugini L, Cecchetti S, Huber V, et al. Immune surveillance properties of human NK cell-derived exosomes. J Immunol 2012; 189(6): 2833-42.
[] [PMID: 22904309]
Li Q, Eades G, Yao Y, Zhang Y, Zhou Q. Characterization of a stem-like subpopulation in basal-like ductal carcinoma in situ (DCIS) lesions. J Biol Chem 2014; 289(3): 1303-12.
[] [PMID: 24297178]
Spanu S, van Roeyen CR, Denecke B, Floege J, Mühlfeld AS. Urinary exosomes: a novel means to non-invasively assess changes in renal gene and protein expression. PLoS One 2014; 9(10) e109631
[] [PMID: 25310591]
Khanabdali R, Rosdah AA, Dusting GJ, Lim SY. Harnessing the secretome of cardiac stem cells as therapy for ischemic heart disease. Biochem Pharmacol 2016; 113: 1-11.
Yun CW, Lee SH. Enhancement of functionality and therapeutic efficacy of cell-based therapy using mesenchymal stem cells for cardiovascular disease. Int J Mol Sci 2019; 20(4) E982
[] [PMID: 30813471]
Yu B, Kim HW, Gong M, et al. Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection. Int J Cardiol 2015; 182: 349-60.
Wei Z, Qiao S, Zhao J, et al. miRNA-181a over-expression in mesenchymal stem cell-derived exosomes influenced inflammatory response after myocardial ischemia-reperfusion injury. Life Sci 2019; 232 116632
Sun XH, Wang X, Zhang Y, Hui J. Exosomes of bone-marrow stromal cells inhibit cardiomyocyte apoptosis under ischemic and hypoxic conditions via miR-486-5p targeting the PTEN/PI3K/AKT signaling pathway. Thromb Res 2019; 177: 23-32.
Cui X, He Z, Liang Z, Chen Z, Wang H, Zhang J. Exosomes from adipose-derived mesenchymal stem cells protect the myocardium against ischemia/reperfusion injury through wnt/beta-catenin signaling pathway. J Cardiovasc Pharmacol 2017; 70(4): 225-31.
[] [PMID: 28582278]
Sheldon H, Heikamp E, Turley H, et al. New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 2010; 116(13): 2385-94.
[] [PMID: 20558614]
Kapustin AN, Shanahan CM. Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation. J Physiol 2016; 594(11): 2905-14.
[] [PMID: 26864864]
Saif J, Emanueli C. miRNAs in post-ischaemic angiogenesis and vascular remodelling. Biochem Soc Trans 2014; 42(6): 1629-36.
[] [PMID: 25399581]
Zhang B, Wang M, Gong A, et al. Hucmsc-exosome mediated-wnt4 signaling is required for cutaneous wound healing. Stem Cells 2015; 33(7): 2158-68.
[] [PMID: 24964196]
Zhang J, Guan J, Niu X, et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J Transl Med 2015; 13: 49.
Zhang J, Chen C, Hu B, et al. Exosomes derived from human endothelial progenitor cells accelerate cutaneous wound healing by promoting angiogenesis through erk1/2 signaling. Int J Biol Sci 2016; 12(12): 1472-87.
[] [PMID: 27994512]
Fang F, Huang RL, Zheng Y, Liu M, Huo R. Bone marrow derived mesenchymal stem cells inhibit the proliferative and profibrotic phenotype of hypertrophic scar fibroblasts and keloid fibroblasts through paracrine signaling. J Dermatol Sci 2016; 83(2): 95-105.
[] [PMID: 27211019]
Wang C, Wang M, Xu T, et al. Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration. Theranostics 2019; 9(1): 65-76.
[] [PMID: 30662554]
Zhang J, Ma J, Long K, et al. Overexpression of exosomal cardioprotective mirnas mitigates hypoxia-induced h9c2 cells apoptosis. Int J Mol Sci 2017; 18(4) E711
[] [PMID: 28350318]
Wang R, Lin M, Li L, et al. [Bone marrow mesenchymal stem cell-derived exosome protects kidney against ischemia reperfusion injury in rats]. Zhonghua Yi Xue Za Zhi 2014; 94(42): 3298-303.
[PMID: 25622627]
Lin KC, Yip HK, Shao PL, et al. Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury. Int J Cardiol 2016; 216: 173-85.
Lv LL, Feng Y, Wu M, et al. Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury. Cell Death Differ 2020; 27: 210-26.
[PMID: 31097789]
Viñas JL, Burger D, Zimpelmann J, et al. Transfer of microRNA-486-5p from human endothelial colony forming cell-derived exosomes reduces ischemic kidney injury. Kidney Int 2016; 90(6): 1238-50.
[] [PMID: 27650731]
Sonoda H, Lee BR, Park KH, et al. miRNA profiling of urinary exosomes to assess the progression of acute kidney injury. Sci Rep 2019; 9(1): 4692.
[] [PMID: 30886169]
Li T, Yan Y, Wang B, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev 2013; 22(6): 845-54.
[] [PMID: 23002959]
Lou G, Song X, Yang F, et al. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. Cytotherapy 2015; 18(12): 1548-59.
Nong K, Wang W, Niu X, et al. Hepatoprotective effect of exosomes from human-induced pluripotent stem cell-derived mesenchymal stromal cells against hepatic ischemia-reperfusion injury in rats. Cytotherapy 2016; 18(12): 1548-59.
[] [PMID: 27592404]
Qu Y, Zhang Q, Cai X, et al. Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation. J Cell Mol Med 2017; 21(10): 2491-502.
[] [PMID: 28382720]
Liu Y, Lou G, Li A, et al. AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages. EBioMedicine 2018; 36: 140-50.
Bucan V, Vaslaitis D, Peck CT, Strauß S, Vogt PM, Radtke C. Effect of exosomes from rat adipose-derived mesenchymal stem cells on neurite outgrowth and sciatic nerve regeneration after crush injury. Mol Neurobiol 2019; 56(3): 1812-24.
[] [PMID: 29931510]
Xin H, Li Y, Liu Z, et al. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells 2013; 31(12): 2737-46.
[] [PMID: 23630198]
Huang S, Ge X, Yu J, et al. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons. FASEB J 2018; 32(1): 512-28.
[] [PMID: 28935818]
Xiao B, Chai Y, Lv S, et al. Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia/reperfusion injury. Int J Mol Med 2017; 40(4): 1201-9.
[] [PMID: 28849073]
Guan J, Zhu Z, Zhao RC, et al. Transplantation of human mesenchymal stem cells loaded on collagen scaffolds for the treatment of traumatic brain injury in rats. Biomaterials 2013; 34(24): 5937-46.
[] [PMID: 23664090]
Sun L, Gao J, Zhao M, et al. The effects of BMSCs transplantation on autophagy by CX43 in the hippocampus following traumatic brain injury in rats. Neurological sciences Official J Italian Neurol Soc Clin Neurophysiol 2014; 35(5): 677-82.
Yin P, Lv H, Li Y, Deng Y, Zhang L, Tang P. Exosome-mediated genetic information transfer, a missing piece of osteoblast-osteoclast communication puzzle. Front Endocrinol (Lausanne) 2017; 8(336): 336.
[] [PMID: 29230197]
Zhou J, Liu HX, Li SH, et al. Effects of human umbilical cord mesenchymal stem cells-derived exosomes on fracture healing in rats through the Wnt signaling pathway. Eur Rev Med Pharmacol Sci 2019; 23(11): 4954-60.
[PMID: 31210331]
Xie Y, Chen Y, Zhang L, Ge W, Tang P. The roles of bone-derived exosomes and exosomal microRNAs in regulating bone remodelling. J Cell Mol Med 2017; 21(5): 1033-41.
[] [PMID: 27878944]
Tao SC, Yuan T, Zhang YL, Yin WJ, Guo SC, Zhang CQ. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics 2017; 7(1): 180-95.
[] [PMID: 28042326]
Wang Y, Zhang L, Li Y, et al. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics 2015; 7(1): 180-95.
Kalani A, Chaturvedi P, Kamat PK, et al. Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury. Intern J Biochem Cell Biol 2016; 79: 360-9.
Mohammadinejad R, Moosavi MA, Tavakol S, et al. Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles. Autophagy 2019; 15(1): 4-33.
[] [PMID: 30160607]
Gross JC, Chaudhary V, Bartscherer K, Boutros M. Active Wnt proteins are secreted on exosomes. Nat Cell Biol 2012; 14(10): 1036-45.
[] [PMID: 22983114]
Harada T, Yamamoto H, Kishida S, et al. Wnt5b-associated exosomes promote cancer cell migration and proliferation. Cancer Sci 2017; 108(1): 42-52.
[] [PMID: 27762090]
Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9(6): 654-9.
[] [PMID: 17486113]
Montecalvo A, Larregina AT, Shufesky WJ, et al. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 2012; 119(3): 756-66.
[] [PMID: 22031862]
Müller G, Schneider M, Biemer-Daub G, Wied S. Microvesicles released from rat adipocytes and harboring glycosylphosphatidylinositol-anchored proteins transfer RNA stimulating lipid synthesis. Cell Signal 2011; 23(7): 1207-23.
[] [PMID: 21435393]
Skog J, Würdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008; 10(12): 1470-6.
[] [PMID: 19011622]
Hurst KV, O’Callaghan JM, Handa A. Quick reference guide to apixaban. Vascular Health Risk Manag 2017; 13: 263-7.
Damania A, Jaiman D, Teotia AK, Kumar A. Mesenchymal stromal cell-derived exosome-rich fractionated secretome confers a hepatoprotective effect in liver injury. Stem Cell Res Ther 2018; 9(1): 31.
[] [PMID: 29409540]
Castaño C, Kalko S, Novials A, Párrizas M. Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice. Proc Natl Acad Sci USA 2018; 115(48): 12158-63.
[] [PMID: 30429322]
Zhu F, Chong Lee Shin OLS, Pei G, et al. Adipose-derived mesenchymal stem cells employed exosomes to attenuate AKI-CKD transition through tubular epithelial cell dependent Sox9 activation. Oncotarget 2017; 8(41): 70707-26.
[] [PMID: 29050313]
Xu HY, Li N, Yao N, et al. CD8+ T cells stimulated by exosomes derived from RenCa cells mediate specific immune responses through the FasL/Fas signaling pathway and, combined with GM‑CSF and IL‑12, enhance the anti‑renal cortical adenocarcinoma effect. Oncol Rep 2019; 42(2): 866-79.
[] [PMID: 31233203]
Li Y, Gao Y, Gong C, et al. A33 antibody-functionalized exosomes for targeted delivery of doxorubicin against colorectal cancer. Nanomedicine (Lond) 2018; 14(7): 1973-85.
[] [PMID: 29935333]
Yang Q, Diamond MP, Al-Hendy A. The emerging role of extracellular vesicle-derived miRNAs: implication in cancer progression and stem cell related diseases. J Clin Epigen 2016; 2(1)
Zhang KL, Wang YJ, Sun J, et al. Artificial chimeric exosomes for anti-phagocytosis and targeted cancer therapy. Chem Sci (Camb) 2018; 10(5): 1555-61.
[] [PMID: 30809374]
Ono M, Kosaka N, Tominaga N, et al. Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci Signal 2014; 7(332): 63.
[] [PMID: 24985346]
Rombouts K, Carloni V, Mello T, et al. Myristoylated Alanine-Rich protein Kinase C Substrate (MARCKS) expression modulates the metastatic phenotype in human and murine colon carcinoma in vitro and in vivo. Cancer Lett 2013; 333(2): 244-52.
[] [PMID: 23376641]
Che Y, Shi X, Shi Y, et al. Exosomes derived from mir-143-overexpressing mscs inhibit cell migration and invasion in human prostate cancer by downregulating tff3. Mol Ther Nucleic Acids 2019; 18: 232-44.
Yu L, Gui S, Liu Y, et al. Exosomes derived from microRNA-199a-overexpressing mesenchymal stem cells inhibit glioma progression by down-regulating AGAP2. Aging (Albany NY) 2019; 11(15): 5300-18.
[] [PMID: 31386624]
Zhang Y, McNeill E, Tian H, et al. Urine derived cells are a potential source for urological tissue reconstruction. J Urol 2008; 180(5): 2226-33.
[] [PMID: 18804817]
Ji X, Wang M, Chen F, Zhou J. Urine-derived stem cells: The present and the future. Stem Cells Int 2017; 2017 4378947
Liu Y, Ma W, Liu B, et al. Urethral reconstruction with autologous urine-derived stem cells seeded in three-dimensional porous small intestinal submucosa in a rabbit model. Stem Cell Res Ther 2017; 8(1): 63.
[] [PMID: 28279224]
Versteegden LRM, de Jonge PKJD, IntHout J, et al. IntHout J, van Kuppevelt TH, Oosterwijk E, Feitz WFJ, de Vries RBM, Daamen WF: tissue engineering of the urethra: a systematic review and meta-analysis of preclinical and clinical studies. Eur Urol 2017; 72(4): 594-606.
[] [PMID: 28385451]
Wang K, Jiang Z, Webster KA, et al. Enhanced cardioprotection by human endometrium mesenchymal stem cells driven by exosomal microrna-21. Stem Cells Transl Med 2017; 6(1): 209-22.
[] [PMID: 28170197]
Xue C, Shen Y, Li X, et al. Exosomes derived from hypoxia-treated human adipose mesenchymal stem cells enhance angiogenesis through the pka signaling pathway. Stem Cells Dev 2018; 27(7): 456-65.
[] [PMID: 29415626]
Dorronsoro A, Robbins PD. Regenerating the injured kidney with human umbilical cord mesenchymal stem cell-derived exosomes. Stem Cell Res Ther 2013; 4(2): 39.
[] [PMID: 23680102]
Mohr A, Lyons M, Deedigan L, et al. Mesenchymal stem cells expressing TRAIL lead to tumour growth inhibition in an experimental lung cancer model. J Cell Mol Med 2008; 12(6B): 2628-43.
[] [PMID: 18373740]
Sodar BW, Kittel A, Paloczi K, et al. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection. Sci Rep 2016; 6 24316
Xie L, Mao M, Zhou L, Jiang B. Spheroid mesenchymal stem cells and mesenchymal stem cell-derived microvesicles: Two potential therapeutic strategies. Stem Cells Dev 2016; 25(3): 203-13.
[] [PMID: 26575103]
Biancone L, Bruno S, Deregibus MC, Tetta C, Camussi G. Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol Dial Transplant 2012; 27(8): 3037-42.
[] [PMID: 22851627]
Zhuang X, Xiang X, Grizzle W, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Molecular therapy J Amn Soc Gene Ther 2011; 19(10): 1769-79.
Ruttala HB, Ko YT. Liposome encapsulated albumin-paclitaxel nanoparticle for enhanced antitumor efficacy. Pharm Res 2015; 32(3): 1002-16.
[] [PMID: 25213777]
Zhang S, Jiang L, Hu H, et al. Pretreatment of exosomes derived from hUCMSCs with TNF-α ameliorates acute liver failure by inhibiting the activation of NLRP3 in macrophage. Life Sci 2020; 246 117401
He X, Dong Z, Cao Y, et al. Msc-derived exosome promotes m2 polarization and enhances cutaneous wound healing. Stem Cells Int 2019. 7132708
Zhu LP, Tian T, Wang JY, et al. Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction. Theranostics 2018; 8(22): 6163-77.
[] [PMID: 30613290]
Liang X, Zhang L, Wang S, Han Q, Zhao RC. Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. J Cell Sci 2016; 129(11): 2182-9.
[] [PMID: 27252357]
Ti D, Hao H, Tong C, et al. LPS-preconditioned mesenchymal stromal cells modify macrophage polarization for resolution of chronic inflammation via exosome-shuttled let-7b. J Transl Med 2015; 13: 308.
Hao SC, Ma H, Niu ZF, Sun SY, Zou YR, Xia HC. hUC-MSCs secreted exosomes inhibit the glioma cell progression through PTENP1/miR-10a-5p/PTEN pathway. Eur Rev Med Pharmacol Sci 2019; 23(22): 10013-23.
[PMID: 31799671]
Shi B, Wang Y, Zhao R, Long X, Deng W, Wang Z. Bone marrow mesenchymal stem cell-derived exosomal miR-21 protects C-kit+ cardiac stem cells from oxidative injury through the PTEN/PI3K/Akt axis. PLoS One 2018; 13(2) e0191616
[] [PMID: 29444190]
Li H, Li F. Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p. Br J Cancer 2018; 119(6): 744-55.
[] [PMID: 30220706]
Mao G, Zhang Z, Hu S, et al. Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A. Stem Cell Res Ther 2018; 9(1): 247.
[] [PMID: 30257711]
Won Lee G, Thangavelu M, Joung Choi M, et al. Exosome mediated transfer of miRNA-140 promotes enhanced chondrogenic differentiation of bone marrow stem cells for enhanced cartilage repair and regeneration. J Cell Biochem 2020. In press.
[] [PMID: 32091634]
Gao S, Chen T, Hao Y, et al. Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression. Stem Cell Res Ther 2020; 11(1): 56.
[] [PMID: 32054526]
Li B, Luan S, Chen J, et al. The msc-derived exosomal lncrna h19 promotes wound healing in diabetic foot ulcers by upregulating pten via microrna-152-3p. Mol Ther Nucleic Acids 2020; 19: 814-26.
Liu Y, Lin L, Zou R, Wen C, Wang Z, Lin F. MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis. Cell Cycle 2018; 17(21-22): 2411-22.
[] [PMID: 30324848]
Li B, Xu H, Han H, et al. Exosome-mediated transfer of lncRUNX2-AS1 from multiple myeloma cells to MSCs contributes to osteogenesis. Oncogene 2018; 37(41): 5508-19.
[] [PMID: 29895968]
Liu Y, Zou R, Wang Z, Wen C, Zhang F, Lin F. Exosomal KLF3-AS1 from hMSCs promoted cartilage repair and chondrocyte proliferation in osteoarthritis. Biochem J 2018; 475(22): 3629-38.
[] [PMID: 30341166]
Yang X, Yang J, Lei P, Wen T. LncRNA MALAT1 shuttled by bone marrow-derived mesenchymal stem cells-secreted exosomes alleviates osteoporosis through mediating microRNA-34c/SATB2 axis. Aging (Albany NY) 2019; 11(20): 8777-91.
[] [PMID: 31659145]
Chen H, Xia W, Hou M. LncRNA-NEAT1 from the competing endogenous RNA network promotes cardioprotective efficacy of mesenchymal stem cell-derived exosomes induced by macrophage migration inhibitory factor via the miR-142-3p/FOXO1 signaling pathway. Stem Cell Res Ther 2020; 11(1): 31.
[] [PMID: 31964409]
Wang Z, Song Y, Han X, Qu P, Wang W. Long noncoding RNA PTENP1 affects the recovery of spinal cord injury by regulating the expression of miR-19b and miR-21. J Cell Physiol 2020; 235(4): 3634-45.
[] [PMID: 31583718]
Zhu B, Zhang L, Liang C, et al. Stem cell-derived exosomes prevent aging-induced cardiac dysfunction through a novel exosome/lncrna malat1/nf-kappab/tnf-alpha signaling pathway. Oxid Med Cell Longev 2019; 2019 9739258
Zhao W, Qin P, Zhang D, et al. Long non-coding RNA PVT1 encapsulated in bone marrow mesenchymal stem cell-derived exosomes promotes osteosarcoma growth and metastasis by stabilizing ERG and sponging miR-183-5p. Aging (Albany NY) 2019; 11(21): 9581-96.
[] [PMID: 31699956]
Huang L, Wang Y, Chen J, et al. Long noncoding RNA PCAT1, a novel serum-based biomarker, enhances cell growth by sponging miR-326 in oesophageal squamous cell carcinoma. Cell Death Dis 2019; 10(7): 513.
[] [PMID: 31273188]
Kahroba H, Davatgaran-Taghipour Y. Exosomal Nrf2: From anti-oxidant and anti-inflammation response to wound healing and tissue regeneration in aged-related diseases. Biochimie 2020; 171-172: 103-9.

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