Engineering mesenchymal stem cells to improve their exosome efficacy and yield for cell-free therapy

References

• Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991 Sep;9(5):1–11. PubMed PMID: 1870029.
   Web of Science ®Google Scholar
• Hass R, Kasper C, Bohm S, et al. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011 May 14;9:12. PubMed PMID: 21569606; PubMed Central PMCID: PMCPMC3117820.
   PubMed Web of Science ®Google Scholar
• Caplan AI. Mesenchymal stem cells: time to change the name! Stem Cells Transl Med. 2017 Jun;6(6):1445–1451. PubMed PMID: 28452204; PubMed Central PMCID: PMCPMC5689741.
   PubMed Web of Science ®Google Scholar
• Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011 Jul 8;9(1):11–15. PubMed PMID: 21726829; PubMed Central PMCID: PMCPMC3144500.
   PubMed Web of Science ®Google Scholar
• Rani S, Ryan AE, Griffin MD, et al. Mesenchymal stem cell-derived extracellular vesicles: toward cell-free therapeutic applications. Mol Therapy: Journal Am Soc Gene Ther. 2015 May;23(5):812–823. PubMed PMID: 25868399; PubMed Central PMCID: PMCPMC4427881. eng.
   PubMed Web of Science ®Google Scholar
• Gnecchi M, Danieli P, Malpasso G, et al. Paracrine mechanisms of mesenchymal stem cells in tissue repair. Methods Molecular Biol (Clifton, NJ). 2016;1416:123–146. PubMed PMID: 27236669; eng.
   PubMedGoogle Scholar
• Liang X, Ding Y, Zhang Y, et al. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplant. 2014;23(9):1045–1059. PubMed PMID: 23676629; eng.
   PubMed Web of Science ®Google Scholar
• Wang A, Brown EG, Lankford L, et al. Placental mesenchymal stromal cells rescue ambulation in ovine myelomeningocele. Stem Cells Transl Med. 2015 Jun;4(6):659–669. PubMed PMID: 25911465; PubMed Central PMCID: PMCPMC4449103. eng.
   Web of Science ®Google Scholar
• Gonzalez-King H, Garcia NA, Ontoria-Oviedo I, et al. Hypoxia inducible factor-1alpha potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes. Stem Cells (Dayton, Ohio). 2017 Jul;35(7):1747–1759. PubMed PMID: 28376567; eng.
   PubMed Web of Science ®Google Scholar
• Salomon C, Ryan J, Sobrevia L, et al. Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis. PLoS One. 2013;8(7):e68451. PubMed PMID: 23861904; PubMed Central PMCID: PMCPMC3704530.
   PubMed Web of Science ®Google Scholar
• 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 Apr 1;27(7):456–465. PubMed PMID: 29415626.
   PubMed Web of Science ®Google Scholar
• Cardenas-Aguayo Mdel C, Kazim SF, Grundke-Iqbal I, et al. Neurogenic and neurotrophic effects of BDNF peptides in mouse hippocampal primary neuronal cell cultures. PloS one. 2013;8(1):e53596. PubMed PMID: 23320097; PubMed Central PMCID: PMCPMC3539976. eng.
   PubMed Web of Science ®Google Scholar
• Liu C, Chan CB, Ye K. 7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders. Transl Neurodegener. 2016 Jan 06;5:2. 09/30/received12/29/accepted. PubMed PMID: PMC4702337.
   PubMed Web of Science ®Google Scholar
• Massa SM, Yang T, Xie Y, et al. Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents. J Clin Invest. 2010 May;120(5):1774–1785. PubMed PMID: 20407211; PubMed Central PMCID: PMCPMC2860903. eng.
   PubMed Web of Science ®Google Scholar
• Jia Y, Shi X, Xie Y, et al. Human umbilical cord stem cell conditioned medium versus serum-free culture medium in the treatment of cryopreserved human ovarian tissues in in-vitro culture: a randomized controlled trial. Stem Cell Res Ther. 2017 Jun 24;8(1):152. PubMed PMID: 28646900; PubMed Central PMCID: PMCPMC5482969. eng.
   Google Scholar
• Lee CY, Kang JY, Lim S, et al. Hypoxic conditioned medium from mesenchymal stem cells promotes lymphangiogenesis by regulation of mitochondrial-related proteins. Stem Cell Res Ther. 2016 Mar 11;7:38. 08/17/received02/15/revised02/22/accepted. PubMed PMID: PMC4788827. .
   Web of Science ®Google Scholar
• Ho JCY, Lai W-H, Li M-F, et al. Reversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell-derived endothelial cells. Diabetes Metab Res Rev. 2012;28(5):462–473.
   Web of Science ®Google Scholar
• Gong M, Yu B, Wang JC, et al. Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis. Oncotarget. 2017 Jul 11;8(28):45200–45212. PubMed PMID: WOS:000405504600020; English.
   PubMedGoogle Scholar
• Mathew SA, Chandravanshi B, Bhonde R. Hypoxia primed placental mesenchymal stem cells for wound healing. Life Sci. 2017 Aug 01;182:85–92.
   Web of Science ®Google Scholar
• Kholia S, Ranghino A, Garnieri P, et al. Extracellular vesicles as new players in angiogenesis. Vascul Pharmacol. 2016 Nov;86:64–70. PubMed PMID: 27013016.
   Web of Science ®Google Scholar
• Burrello J, Monticone S, Gai C, et al. Stem cell-derived extracellular vesicles and immune-modulation. Front Cell Dev Biol. 2016;4:83. PubMed PMID: 27597941; PubMed Central PMCID: PMCPMC4992732.
   PubMed Web of Science ®Google Scholar
• Eitan E, Suire C, Zhang S, et al. Impact of lysosome status on extracellular vesicle content and release. Ageing Res Rev. 2016 Dec;32:65–74. PubMed PMID: WOS:000390623400007; English.
   PubMed Web of Science ®Google Scholar
• Escudero CA, Lazo OM, Galleguillos C, et al. The p75 neurotrophin receptor evades the endolysosomal route in neuronal cells, favouring multivesicular bodies specialised for exosomal release. J Cell Sci. 2014 May 01;127(Pt 9):1966–1979. PubMed PMID: 24569882; PubMed Central PMCID: PMCPMC4004974. eng.
   Web of Science ®Google Scholar
• Marote A, Teixeira FG, Mendes-Pinheiro B, et al. MSCs-derived exosomes: cell-secreted nanovesicles with regenerative potential. Front Pharmacol. 2016;7:231. PubMed PMID: 27536241; PubMed Central PMCID: PMCPMC4971062.
   PubMed Web of Science ®Google Scholar
• Nawaz M, Camussi G, Valadi H, et al. The emerging role of extracellular vesicles as biomarkers for urogenital cancers. Nat Rev Urol. 2014 Dec;11(12):688–701. PubMed PMID: WOS:000345908700006; English.
   PubMed Web of Science ®Google Scholar
• Urbanelli L, Magini A, Buratta S, et al. Signaling pathways in exosomes biogenesis, secretion and fate. Genes (Basel). 2013 Mar 28;4(2):152–170. PubMed PMID: 24705158; PubMed Central PMCID: PMCPMC3899971.
   PubMed Web of Science ®Google Scholar
• Coumans FAW, Brisson AR, Buzas EI, et al. Methodological guidelines to study extracellular vesicles. Circ Res. 2017 May 12;120(10):1632–1648. PubMed PMID: 28495994.
   PubMed Web of Science ®Google Scholar
• Mateescu B, Kowal EJ, van Balkom BW, et al. Obstacles and opportunities in the functional analysis of extracellular vesicle RNA - an ISEV position paper. J Extracell Vesicles. 2017;6(1):1286095. PubMed PMID: 28326170; PubMed Central PMCID: PMCPMC5345583.
   PubMed Web of Science ®Google Scholar
• Ramirez MI, Amorim MG, Gadelha C, et al. Technical challenges of working with extracellular vesicles. Nanoscale. 2018 Jan 18;10(3):881–906. PubMed PMID: 29265147.
   PubMed Web of Science ®Google Scholar
• Gyorgy B, Szabo TG, Pasztoi M, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Molecular Life Sci: CMLS. 2011 Aug;68(16):2667–2688. PubMed PMID: 21560073; PubMed Central PMCID: PMCPMC3142546. eng.
   PubMed Web of Science ®Google Scholar
• Hao D, Xiao W, Liu R, et al. Discovery and characterization of a potent and specific peptide ligand targeting endothelial progenitor cells and endothelial cells for tissue regeneration. ACS Chem Biol. 2017 Apr 21;12(4):1075–1086. PubMed PMID: 28195700; eng.
   Web of Science ®Google Scholar
• Tao SC, Guo SC, Li M, et al. Chitosan wound dressings incorporating exosomes derived from microRNA-126-overexpressing synovium mesenchymal stem cells provide sustained release of exosomes and heal full-thickness skin defects in a diabetic rat model. Stem Cells Transl Med. 2017 Mar;6(3):736–747. PubMed PMID: 28297576; PubMed Central PMCID: PMCPMC5442792. eng.
   PubMed Web of Science ®Google Scholar
• Bai L, Shao H, Wang H, et al. Effects of mesenchymal stem cell-derived exosomes on experimental autoimmune uveitis. Sci Rep. 2017 Jun 28;7(1):4323. PubMed PMID: 28659587; PubMed Central PMCID: PMCPMC5489510. eng.
   PubMed Web of Science ®Google Scholar
• Lasser C, Jang SC, Lotvall J. Subpopulations of extracellular vesicles and their therapeutic potential. Mol Aspects Med. 2018 Apr;60:1–14. PubMed PMID: 29432782; eng.
   Web of Science ®Google Scholar
• Lai RC, Tan SS, Yeo RW, et al. MSC secretes at least 3 EV types each with a unique permutation of membrane lipid, protein and RNA. J Extracell Vesicles. 2016;5:29828. PubMed PMID: 26928672; PubMed Central PMCID: PMCPMC4770866.
   PubMed Web of Science ®Google Scholar
• Pegtel DM, Peferoen L, Amor S. Extracellular vesicles as modulators of cell-to-cell communication in the healthy and diseased brain. PubMed PMID: PMC4142037 Philosophical Trans Royal Soc B: Biol Sci. 2014;3691652:20130516.
   Web of Science ®Google Scholar
• Yáñez-Mó M, Siljander PRM, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracellular Vesicles. 2015 May 14;4. 12/22/received02/24/revised03/10/accepted doi:10.3402/jev.v4.27066. PubMed PMID: PMC4433489
   Web of Science ®Google Scholar
• Xin H, Li Y, Chopp M. Exosomes/miRNAs as mediating cell-based therapy of stroke [Review]. Front Cell Neurosci. 2014 2014 Nov 10; 8(377): doi:10.3389/fncel.2014.00377. English
   Web of Science ®Google Scholar
• Pachler K, Lener T, Streif D, et al. A good manufacturing practice-grade standard protocol for exclusively human mesenchymal stromal cell-derived extracellular vesicles. Cytotherapy. 2017 Apr;19(4):458–472. PubMed PMID: 28188071.
   PubMed Web of Science ®Google Scholar
• Luan X, Sansanaphongpricha K, Myers I, et al. Engineering exosomes as refined biological nanoplatforms for drug delivery [Review]. Acta Pharmacologica Sinica. 2017;38:754. 04/10/online.
   PubMed Web of Science ®Google Scholar
• Willis GR, Kourembanas S, Mitsialis SA. Toward exosome-based therapeutics: isolation, heterogeneity, and fit-for-purpose potency. Front Cardiovasc Med. 2017 Oct 09;4:63. 07/10/received09/25/accepted. PubMed PMID: PMC5640880.
   PubMed Web of Science ®Google Scholar
• Ferguson SW, Wang J, Lee CJ, et al. The microRNA regulatory landscape of MSC-derived exosomes: a systems view. Sci Rep. 2018;8(1):1419.
   PubMed Web of Science ®Google Scholar
• Bagno L, Hatzistergos KE, Balkan W, et al. Mesenchymal stem cell-based therapy for cardiovascular disease: progress and challenges. Mol Therapy: Journal Am Soc Gene Ther. 2018 Jul 5;26(7):1610–1623. PubMed PMID: 29807782; PubMed Central PMCID: PMCPMC6037203. eng.
   PubMed Web of Science ®Google Scholar
• Cha JM, Shin EK, Sung JH, et al. Efficient scalable production of therapeutic microvesicles derived from human mesenchymal stem cells. Sci Rep. 2018 Jan 19;8(1):1171. PubMed PMID: 29352188; PubMed Central PMCID: PMCPMC5775399. eng.
   PubMedGoogle Scholar
• Kim HY, Kumar H, Jo M-J, et al. Therapeutic efficacy-potentiated and diseased organ-targeting nanovesicles derived from mesenchymal stem cells for spinal cord injury treatment. Nano Letters. 2018 2018 Jul 11. DOI:10.1021/acs.nanolett.8b01816.
   Web of Science ®Google Scholar
• Cheng L, Zhang K, Wu S, et al. Focus on mesenchymal stem cell-derived exosomes: opportunities and challenges in cell-free therapy. Stem Cells Int. 2017 Dec 19;2017:6305295. 08/11/received11/05/revised11/22/accepted. PubMed PMID: PMC5749272.
   PubMed Web of Science ®Google Scholar
• Du W, Zhang K, Zhang S, et al. Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes stimulated by a nitric oxide releasing polymer. Biomaterials. 2017 Jul;133:70–81. PubMed PMID: 28433939; eng.
   PubMed Web of Science ®Google Scholar
• Huleihel L, Hussey GS, Naranjo JD, et al. Matrix-bound nanovesicles within ECM bioscaffolds. Sci Adv. 2016 Jun;2(6):e1600502. PubMed PMID: 27386584; PubMed Central PMCID: PMCPMC4928894.
   PubMed Web of Science ®Google Scholar
• Qazi TH, Mooney DJ, Duda GN, et al. Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs. Biomaterials. 2017 Sep;140:103–114. PubMed PMID: 28644976; eng.
   PubMed Web of Science ®Google Scholar
• Su N, Gao PL, Wang K, et al. Fibrous scaffolds potentiate the paracrine function of mesenchymal stem cells: a new dimension in cell-material interaction. Biomaterials. 2017 Oct;141:74–85. PubMed PMID: 28667901; eng.
   PubMed Web of Science ®Google Scholar
• Hanley PJ, Mei ZY, Durett AG, et al. Efficient manufacturing of therapeutic mesenchymal stromal cells with the use of the quantum cell expansion system. Cytotherapy. 2014 Aug;16(8):1048–1058. PubMed PMID: WOS:000338819200003; English.
   PubMed Web of Science ®Google Scholar
• Panchalingam KM, Jung S, Rosenberg L, et al. Bioprocessing strategies for the large-scale production of human mesenchymal stem cells: a review. Stem Cell Res Ther. 2015 Nov 23;6:225. doi:10.1186/s13287-015-0228-5. PubMed PMID: 26597928; PubMed Central PMCID: PMCPMC4657237.
   PubMed Web of Science ®Google Scholar
• Petry F, Smith JR, Leber J, et al. Manufacturing of human umbilical cord mesenchymal stromal cells on microcarriers in a dynamic system for clinical use. Stem Cells Int. 2016. doi:10.1155/2016/4834616. PubMed PMID: WOS:000373501800001; English
   Web of Science ®Google Scholar
• Rafiq QA, Coopman K, Nienow AW, et al. Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors. Biotechnol J. 2016 Mar;11(4):473–486. PubMed PMID: 26632496; PubMed Central PMCID: PMCPMC4991290. eng.
   Web of Science ®Google Scholar
• Teixeira FG, Panchalingam KM, Assuncao-Silva R, et al. Modulation of the mesenchymal stem cell secretome using computer-controlled bioreactors: impact on neuronal cell proliferation, survival and differentiation. Sci Rep-Uk. 2016 Jun 15;6:27791. PubMed PMID: WOS:000384559600001; English.
   Web of Science ®Google Scholar
• Lechanteur C, Briquet A, Giet O, et al. Clinical-scale expansion of mesenchymal stromal cells: a large banking experience. J Transl Med. 2016 May 20;14(1):145. PubMed PMID: 27207011; PubMed Central PMCID: PMCPMC4875672.
   PubMed Web of Science ®Google Scholar
• Yan IK, Shukla N, Borrelli DA, et al. Use of a hollow fiber bioreactor to collect extracellular vesicles from cells in culture. Methods Molecular Biol (Clifton, NJ). 2018;1740:35–41. PubMed PMID: 29388134; eng.
   Google Scholar
• Qu Y, Dubyak GR. P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways. Purinergic Signal. 2009 Feb 03 05/26/received;5(2):163–173. . PubMed PMID: PMC2686822.
   Web of Science ®Google Scholar
• Colombo M, Raposo G, Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255–289. PubMed PMID: 25288114.
   PubMed Web of Science ®Google Scholar
• Fader CM, Sanchez DG, Mestre MB, et al. TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim Biophys Acta. 2009 Dec;1793(12):1901–1916. PubMed PMID: 19781582.
   PubMed Web of Science ®Google Scholar
• Rao SK, Huynh C, Proux-Gillardeaux V, et al. Identification of SNAREs involved in synaptotagmin VII-regulated lysosomal exocytosis. J Biol Chem. 2004 May 7;279(19):20471–20479. PubMed PMID: 14993220.
   PubMed Web of Science ®Google Scholar
• Lespagnol A, Duflaut D, Beekman C, et al. Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice. Cell Death Differ. 2008 Nov;15(11):1723–1733. PubMed PMID: 18617898; eng.
   PubMed Web of Science ®Google Scholar
• Yu X, Harris SL, Levine AJ. The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res. 2006 May 01;66(9):4795–4801. . PubMed PMID: 16651434; eng.
   PubMed Web of Science ®Google Scholar
• Wan C, Fu J, Wang Y, et al. Exosome-related multi-pass transmembrane protein TSAP6 is a target of rhomboid protease RHBDD1-induced proteolysis. PloS one. 2012;7(5):e37452. PubMed PMID: 22624035; PubMed Central PMCID: PMCPMC3356283. eng.
   Web of Science ®Google Scholar
• Laulagnier K, Grand D, Dujardin A, et al. PLD2 is enriched on exosomes and its activity is correlated to the release of exosomes. FEBS letters. 2004 Aug 13;572(1–3):11–14. PubMed PMID: 15304316; eng.
   PubMed Web of Science ®Google Scholar
• Hsu C, Morohashi Y, Yoshimura S, et al. Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol. 2010 Apr 19;189(2):223–232. PubMed PMID: 20404108; PubMed Central PMCID: PMCPMC2856897. eng.
   PubMed Web of Science ®Google Scholar
• Ostrowski M, Carmo NB, Krumeich S, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2010 Jan;12(1):19–30. PubMed PMID: 19966785.
   PubMed Web of Science ®Google Scholar
• Fatima F, Ekstrom K, Nazarenko I, et al. Non-coding RNAs in mesenchymal stem cell-derived extracellular vesicles: deciphering regulatory roles in stem cell potency, inflammatory resolve, and tissue regeneration. Front Genet. 2017;8:161. PubMed PMID: 29123544; PubMed Central PMCID: PMCPMC5662888.
   Web of Science ®Google Scholar
• Ma J, Zhao Y, Sun L, et al. Exosomes derived from AKT-modified human umbilical cord mesenchymal stem cells improve cardiac regeneration and promote angiogenesis via activating platelet-derived growth factor D. Stem Cells Transl Med. 2017 Jan;6(1):51–59. PubMed PMID: 28170176; PubMed Central PMCID: PMCPMC5442756. eng.
   PubMed Web of Science ®Google Scholar
• Malik SZ, Motamedi S, Royo NC, et al. Identification of potentially neuroprotective genes upregulated by neurotrophin treatment of CA3 neurons in the injured brain. J Neurotrauma. 2011 Mar;28(3):415–430. PubMed PMID: 21083427; PubMed Central PMCID: PMCPMC3057196. eng.
   PubMed Web of Science ®Google Scholar
• Ti DD, Hao HJ, Fu XB, et al. Mesenchymal stem cells-derived exosomal microRNAs contribute to wound inflammation. Sci China Life Sci. 2016 Dec;59(12):1305–1312. PubMed PMID: WOS:000390669100012; English.
   PubMed Web of Science ®Google Scholar
• 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 (Dayton, Ohio). 2013 Dec;31(12):2737–2746. PubMed PMID: 23630198; PubMed Central PMCID: PMCPMC3788061. eng.
   PubMed Web of Science ®Google Scholar
• Mayourian J, Ceholski DK, Gorski PA, et al. Exosomal microRNA-21-5p mediates mesenchymal stem cell paracrine effects on human cardiac tissue contractility. Circ Res. 2018 Mar 30;122(7):933–944. PubMed PMID: 29449318.
   PubMed Web of Science ®Google Scholar
• Mathiyalagan P, Sahoo S. Exosomes-based gene therapy for microRNA delivery. Methods Mol Biol. 2017;1521:139–152. PubMed PMID: 27910046; PubMed Central PMCID: PMCPMC5502074.
   PubMedGoogle Scholar
• Lener T, Gimona M, Aigner L, et al. Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper. J Extracell Vesicles. 2015;4:30087. PubMed PMID: 26725829; PubMed Central PMCID: PMCPMC4698466.
   PubMed Web of Science ®Google Scholar