Stem cell-derived extracellular vesicle therapy for acute brain insults and neurodegenerative diseases
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Stem cell-based therapy is a promising approach for treating avariety of disorders, including acute brain insults and neurodegenerativediseases. Stem cells such as mesenchymal stem cells(MSCs) secrete extracellular vesicles (EVs), circular membranefragments (30 nm−1 μm) that are shed from the cell surface,carrying several therapeutic molecules such as proteins andmicroRNAs. Because EV-based therapy is superior to cell therapyin terms of scalable production, biodistribution, and safetyprofiles, it can be used to treat brain diseases as an alternativeto stem cell therapy. This review presents evidences evaluatingthe role of stem cell-derived EVs in stroke, traumatic braininjury, and degenerative brain diseases, such as Alzheimer’sdisease and Parkinson’ disease. In addition, stem cell-derivedEVs have better profiles in biocompatibility, immunogenicity,and safety than those of small chemical and macromolecules. The advantages and disadvantages of EVs compared with otherstrategies are discussed. Even though EVs obtained from nativestem cells have potential in the treatment of brain diseases, thesuccessful clinical application is limited by the short half-life,limited targeting, rapid clearance after application, and insufficientpayload. We discuss the strategies to enhance the efficacyof EV therapeutics. Finally, EV therapies have yet to be approvedby the regulatory authorities. Major issues are discussed togetherwith relevant advances in the clinical application of EV therapeutics.
Abstract
Stem cell-based therapy is a promising approach for treating avariety of disorders, including acute brain insults and neurodegenerativediseases. Stem cells such as mesenchymal stem cells(MSCs) secrete extracellular vesicles (EVs), circular membranefragments (30 nm−1 μm) that are shed from the cell surface,carrying several therapeutic molecules such as proteins andmicroRNAs. Because EV-based therapy is superior to cell therapyin terms of scalable production, biodistribution, and safetyprofiles, it can be used to treat brain diseases as an alternativeto stem cell therapy. This review presents evidences evaluatingthe role of stem cell-derived EVs in stroke, traumatic braininjury, and degenerative brain diseases, such as Alzheimer’sdisease and Parkinson’ disease. In addition, stem cell-derivedEVs have better profiles in biocompatibility, immunogenicity,and safety than those of small chemical and macromolecules. The advantages and disadvantages of EVs compared with otherstrategies are discussed. Even though EVs obtained from nativestem cells have potential in the treatment of brain diseases, thesuccessful clinical application is limited by the short half-life,limited targeting, rapid clearance after application, and insufficientpayload. We discuss the strategies to enhance the efficacyof EV therapeutics. Finally, EV therapies have yet to be approvedby the regulatory authorities. Major issues are discussed togetherwith relevant advances in the clinical application of EV therapeutics.
참고문헌 (106)
- Bang OY, "Neuroprotective strategies for acute ischemic stroke : recent progress and future perspectives", Precis Future Med, 1, pp.115~121 (2017)
- Kordower JH, "Trophic factor gene therapy for Parkinson’s disease", Mov Disord, 28, pp.96~109 (2013)
- Lo EH, "A new penumbra : transitioning from injury into repair after stroke", Nat Med, 14, pp.497~500 (2008)
- Lyden PD, "Cerebroprotection for acute ischemic stroke : looking ahead", Stroke, 52, pp.3033~3044 (2021)
- Rufino-Ramos D, "Extracellular vesicles : novel promising delivery systems for therapy of brain diseases", J Control Release, 262, pp.247~258 (2017)
- Lee JS, "A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke", Stem Cells, 28, pp.1099~1106 (2010)
- Prasad K, "Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic stroke : a multicentric, randomized trial", Stroke, 45, pp.3618~3624 (2014)
- Hess DC, "Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke(MASTERS) : a randomised, doubleblind, placebo-controlled, phase 2 trial", Lancet Neurol, 16, pp.360~368 (2017)
- Chung JW, "Efficacy and safety of intravenous mesenchymal stem cells for ischemic stroke", Neurology, 96, pp.e1012~ (2021)
- Zagrean AM, "Multicellular crosstalk between exosomes and the neurovascular unit after cerebral ischemia. Therapeutic implications", Front Neurosci, 12, pp.811~ (2018)
- Brites D, "Regulatory function of microRNAs in microglia", Glia, 68, pp.1631~1642 (2020)
- Choi Y, "Nanoelectrical characterization of individual exosomes secreted by Abeta42-ingested cells using electrostatic force microscopy", Nanotechnology, 32, pp.025705~ (2021)
- Crewe C, "Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes", Cell Metab, 33, pp.1853~1868 (2021)
- O’Brien CG, "Mitochondria-rich extracellular vesicles rescue patient-specific cardiomyocytes from doxorubicin injury : insights into the SENECA trial", JACC CardioOncol, 3, pp.428~440 (2021)
- D’Souza A, "Microvesicles transfer mitochondria and increase mitochondrial function in brain endothelial cells", J Control Release, 338, pp.505~526 (2021)
- Nam GH, "Emerging prospects of exosomes for cancer treatment : from conventional therapy to immunotherapy", Adv Mater, 32, pp.e2002440~ (2020)
- Otero-Ortega L, "Low dose of extracellular vesicles identified that promote recovery after ischemic stroke", Stem Cell Res Ther, 11, pp.70~ (2020)
- Wen S, "Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a radiation injury bone marrow murine model", Int J Mol Sci, 20, pp.5468~ (2019)
- Mirzaaghasi A, "Biodistribution and pharmacokinectics of liposomes and exosomes in a mouse model of sepsis", Pharmaceutics, 13, pp.427~ (2021)
- Lai RC, "Proteolytic potential of the MSc exosome proteome : implications for an exosome-mediated delivery of therapeutic proteasome", Int J Proteomics, 2012, pp.971907~ (2012)
- Biancone L, "Therapeutic potential of mesenchymal stem cell-derived microvesicles", Nephrol Dial Transplant, 27, pp.3037~3042 (2012)
- Karp JM, "Mesenchymal stem cell homing : the devil is in the details", Cell Stem Cell, 4, pp.206~216 (2009)
- Le Saux S, "Interest of extracellular vesicles in regards to lipid nanoparticle based systems for intracellular protein delivery", Adv Drug Deliv Rev, 176, pp.113837~ (2021)
- Muhammad SA, "Comparative efficacy of stem cells and secretome in articular cartilage regeneration : a systematic review and meta-analysis", Cell Tissue Res, 375, pp.329~344 (2019)
- Zheng X, "The role of small extracellular vesicles in cerebral and myocardial ischemia-Molecular signals, treatment targets, and future clinical translation", Stem Cells, 39, pp.403~413 (2021)
- Cai J, "Extracellular vesicles derived from different sources of mesenchymal stem cells : therapeutic effects and translational potential", Cell Biosci, 10, pp.69~ (2020)
- Loukogeorgakis SP, "Concise review : amniotic fluid stem cells : the known, the unknown, and potential regenerative medicine applications", Stem Cells, 35, pp.1663~1673 (2017)
- Johnson J, "From mesenchymal stromal cells to engineered extracellular vesicles : a new therapeutic paradigm", Front Cell Dev Biol, 9, pp.705676~ (2021)
- Upadhya R, "Extracellular vesicles from human iPSC-derived neural stem cells : miRNA and protein signatures, and anti-inflammatory and neurogenic properties", J Extracell Vesicles, 9, pp.1809064~ (2020)
- Webb RL, "Human neural stem cell extracellular vesicles improve tissue and functional recovery in the murine thromboembolic stroke model", Transl Stroke Res, 9, pp.530~539 (2018)
- Bang OY, "Mesenchymal stem cell-derived extracellular vesicle therapy for stroke : challenges and progress", Front Neurol, 10, pp.211~ (2019)
- Xin H, "Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats", J Cereb Blood Flow Metab, 33, pp.1711~1715 (2013)
- Kalani A, "Curcuminloaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury", Int J Biochem Cell Biol, 79, pp.360~369 (2016)
- Webb RL, "Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke", Stroke, 49, pp.1248~1256 (2018)
- Cha JM, "Efficient scalable production of therapeutic microvesicles derived from human mesenchymal stem cells", Sci Rep, 8, pp.1171~ (2018)
- Moon GJ, "Application of mesenchymal stem cell-derived extracellular vesicles for stroke : biodistribution and microRNA Study", Transl Stroke Res, 10, pp.509~521 (2019)
- Lee JY, "Microvesicles from brain-extract-treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke", Sci Rep, 6, pp.33038~ (2016)
- Medalla M, "Treatment with mesenchymal-derived extracellular vesicles reduces injury-related pathology in pyramidal neurons of monkey perilesional ventral premotor cortex", J Neurosci, 40, pp.3385~3407 (2020)
- Gao W, "Endothelial colonyforming cell-derived exosomes restore blood-brain barrier continuity in mice subjected to traumatic brain injury", Exp Neurol, 307, pp.99~108 (2018)
- Chen W, "Astrocytesderived exosomes induce neuronal recovery after traumatic brain injury via delivering gap junction alpha 1-20 k", J Tissue Eng Regen Med, 14, pp.412~423 (2020)
- Zhang Y, "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, 111, pp.69~81 (2017)
- Williams AM, "Early single-dose treatment with exosomes provides neuroprotection and improves blood-brain barrier integrity in swine model of traumatic brain injury and hemorrhagic shock", J Trauma Acute Care Surg, 88, pp.207~218 (2020)
- Yin Z, "Neuron-derived exosomes with high miR-21-5p expression promoted polarization of M1 microglia in culture", Brain Behav Immun, 83, pp.270~282 (2020)
- Long X, "Astrocyte-derived exosomes enriched with miR-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury", J Neuroinflammation, 17, pp.89~ (2020)
- Soares Martins T, "Diagnostic and therapeutic potential of exosomes in Alzheimer’s disease", J Neurochem, 156, pp.162~181 (2021)
- Elia CA, "Intracerebral injection of extracellular vesicles from mesenchymal stem cells exerts reduced abeta plaque burden in early stages of a preclinical model of Alzheimer’s disease", Cells, 8, pp.1059~ (2019)
- Losurdo M, "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, 9, pp.1068~1084 (2020)
- Ma X, "ADSCs-derived extracellular vesicles alleviate neuronal damage, promote neurogenesis and rescue memory loss in mice with Alzheimer’s disease", J Control Release, 327, pp.688~702 (2020)
- Cone AS, "Mesenchymal stem cell-derived extracellular vesicles ameliorate Alzheimer’s disease-like phenotypes in a preclinical mouse model", Theranostics, 11, pp.8129~8142 (2021)
- Cui GH, "Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP", PS1 mice, 2018, pp.32, 654~668
- Narbute K, "Intranasal administration of extracellular vesicles derived from human teeth stem cells improves motor symptoms and normalizes tyrosine hydroxylase expression in the substantia nigra and striatum of the 6-Hydroxydopaminetreated rats", Stem Cells Transl Med, 8, pp.490~499 (2019)
- Cui GH, "Effects of exosomal miRNAs in the diagnosis and treatment of Alzheimer’s disease", Mech Ageing Dev, 200, pp.111593~ (2021)
- Katsuda T, "Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes", Sci Rep, 3, pp.1197~ (2013)
- Li X, "Puerarin suppresses MPP(+)", MPTP-induced oxidative stress through an Nrf2-dependent mechanism, 2020, pp.144, 111644~
- Izco M, "Systemic exosomal delivery of shRNA minicircles prevents parkinsonian pathology", Mol Ther, 27, pp.2111~2122 (2019)
- Chen HX, "Exosomes derived from mesenchymal stem cells repair a Parkinson’s disease model by inducing autophagy", Cell Death Dis, 11, pp.288~ (2020)
- Akkoc Y, "MicroRNAs as major regulators of the autophagy pathway", Biochim Biophys Acta Mol Cell Res, 1867, pp.118662~ (2020)
- Jeon I, "Human-tomouse prion-like propagation of mutant huntingtin protein", Acta Neuropathol, 132, pp.577~592 (2016)
- Didiot MC, "Exosomemediated delivery of hydrophobically modified siRNA for Huntingtin mRNA silencing", Mol Ther, 24, pp.1836~1847 (2016)
- Wang C, "Mesenchymal stromal cell-derived small extracellular vesicles induce ischemic neuroprotection by modulating leukocytes and specifically neutrophils", Stroke, 51, pp.1825~1834 (2020)
- Costa LA, "Functional heterogeneity of mesenchymal stem cells from natural niches to culture conditions : implications for further clinical uses", Cell Mol Life Sci, 78, pp.447~467 (2021)
- de Almeida Fuzeta M, "Scalable production of human mesenchymal stromal cell-derived extracellular vesicles under serum-", xenofree conditions in a microcarrier-based bioreactor culture system, 2020, pp.8, 553444~
- Nalamolu KR, "Exosomes treatment mitigates ischemic brain damage but does not improve post-stroke neurological outcome", Cell Physiol Biochem, 52, pp.1280~1291 (2019)
- Khan H, "Native and bioengineered exosomes for ischemic stroke therapy", Front Cell Dev Biol, 9, pp.619565~ (2021)
- Chen CC, "Elucidation of exosome migration across the blood-brain barrier model in vitro", Cell Mol Bioeng, 9, pp.509~529 (2016)
- Yuan D, "Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain", Biomaterials, 142, pp.1~12 (2017)
- Wiklander OP, "Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting", J Extracell Vesicles, 4, pp.26316~ (2015)
- Gholamrezanezhad A, "In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis", Nucl Med Biol, 38, pp.961~967 (2011)
- Banks WA, "Transport of extracellular vesicles across the blood-brain barrier : brain pharmacokinetics and effects of inflammation", Int J Mol Sci, 21, pp.4407~ (2020)
- Saint-Pol J, "Targeting and crossing the bloodbrain barrier with extracellular vesicles", Cells, 9, pp.851~ (2020)
- Zhao Z, "Remote control of BBB : A tale of exosomes and microRNA", Cell Res, 27, pp.849~850 (2017)
- Zhao C, "Hypoxic glioblastoma release exosomal VEGF-A induce the permeability of blood-brain barrier", Biochem Biophys Res Commun, 502, pp.324~331 (2018)
- Durcin M, "Characterisation of adipocyte-derived extracellular vesicle subtypes identifies distinct protein and lipid signatures for large and small extracellular vesicles", J Extracell Vesicles, 6, pp.1305677~ (2017)
- Wei Z, "Mononuclear phagocyte system blockade using extracellular vesicles modified with CD47 on membrane surface for myocardial infarction reperfusion injury treatment", Biomaterials, 275, pp.121000~ (2021)
- Daniel E. Murphy, "Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking", Experimental and Molecular Medicine, 51, pp.1~12 (2019), 생화학분자생물학회[DOI]
- Cunningham CJ, "The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke", J Cereb Blood Flow Metab, 38, pp.1276~1292 (2018)
- Park KS, "Enhancement of therapeutic potential of mesenchymal stem cell-derived extracellular vesicles", Stem Cell Res Ther, 10, pp.288~ (2019)
- Millan C, "Extracellular vesicles from 3D engineered microtissues harbor disease-related cargo absent in EVs from 2D cultures", Adv Healthc Mater, pp.e2002067~ (2021)
- Pauwels MJ, "Special delEVery : extracellular vesicles as promising delivery platform to the brain", Biomedicines, 9, pp.1734~ (2021)
- Wiklander OPB, "Advances in therapeutic applications of extracellular vesicles", Sci Transl Med, 11, pp.eaav8521~ (2019)
- Lino MM, "Engineered extracellular vesicles as brain therapeutics", J Control Release, 338, pp.472~485 (2021)
- Pedrioli G, "Extracellular vesicles as promising carriers in drug delivery : considerations from a cell biologist’s perspective", Biology(Basel), 10, pp.376~ (2021)
- Crescitelli R, "Distinct RNA profiles in subpopulations of extracellular vesicles : apoptotic bodies, microvesicles and exosomes", J Extracell Vesicles, 2, pp.1~10 (2013)
- Zhang ZG, "Exosomes-beyond stem cells for restorative therapy in stroke and neurological injury", Nat Rev Neurol, 15, pp.193~203 (2019)
- Yang J, "Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia", Mol Ther Nucleic Acids, 7, pp.278~287 (2017)
- Xin H, "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, 31, pp.2737~2746 (2013)
- Xin H, "MicroRNA cluster miR-17-92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats", Stroke, 48, pp.747~753 (2017)
- D’Souza A, "Targeting the blood-brain barrier for the delivery of stroke therapies", Adv Drug Deliv Rev, 171, pp.332~351 (2021)
- Poo MM, "Neurotrophins as synaptic modulators", Nat Rev Neurosci, 2, pp.24~32 (2001)
- Ahn EH, "Netrin-1", receptors regulate the pathogenesis in Parkinson’s diseases, 2021, pp.5, 50~61
- Yang J, "Therapeutic effects of simultaneous delivery of nerve growth factor mRNA and protein via exosomes on cerebral ischemia", Mol Ther Nucleic Acids, 21, pp.512~522 (2020)
- Zha Y, "Progenitor cell-derived exosomes endowed with VEGF plasmids enhance osteogenic induction and vascular remodeling in large segmental bone defects", Theranostics, 11, pp.397~409 (2021)
- Haney MJ, "Exosomes as drug delivery vehicles for Parkinson’s disease therapy", J Control Release, 207, pp.18~30 (2015)
- Kang JY, "Co-delivery of curcumin and miRNA-144-3p using hearttargeted extracellular vesicles enhances the therapeutic efficacy for myocardial infarction", J Control Release, 331, pp.62~73 (2021)
- Li S, "Curcumin-primed human BMSC-derived extracellular vesicles reverse IL-1beta-induced catabolic responses of OA chondrocytes by upregulating miR-126-3p", Stem Cell Res Ther, 12, pp.252~ (2021)
- 함주희, "Strategies to Enhance Extracellular Vesicle Production", 조직공학과 재생의학, 18(4), pp.513~524 (2021), 한국조직공학과 재생의학회[DOI]
- Grangier A, "Technological advances towards extracellular vesicles mass production", Adv Drug Deliv Rev, 176, pp.113843~ (2021)
- Haraszti RA, "Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity", Mol Ther, 26, pp.2838~2847 (2018)
- Kordelas L, "MSCderived exosomes : a novel tool to treat therapy-refractory graft-versus-host disease", Leukemia, 28, pp.970~973 (2014)
- Wael Nassar, "Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases", 생체재료학회지, 20(3), pp.200~210 (2016), 한국생체재료학회[DOI]
- Sengupta V, "Exosomes derived from bone marrow mesenchymal stem cells as treatment for severe COVID-19", Stem Cells Dev, 29, pp.747~754 (2020)
- Katagiri W, "First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells", Head Face Med, 12, pp.5~ (2016)
- Fukuoka H, "Hair regeneration treatment using adipose-derived stem cell conditioned medium : follow-up with trichograms", Eplasty, 15, pp.e10~ (2015)
- Warnecke A, "First-inhuman intracochlear application of human stromal cellderived extracellular vesicles", J Extracell Vesicles, 10, pp.e12094~ (2021)
- Zhang X, "Effects of mesenchymal stem cells and their exosomes on the healing of large and refractory macular holes", Graefes Arch Clin Exp Ophthalmol, 256, pp.2041~2052 (2018)
- Szebeni J, "Activation of complement by therapeutic liposomes and other lipid excipient-based therapeutic products : prediction and prevention", Adv Drug Deliv Rev, 63, pp.1020~1030 (2011)
