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Review

In vitro models of neuromuscular junctions and their potential for novel drug discovery and development

, &
Pages 307-317 | Received 01 Oct 2019, Accepted 29 Nov 2019, Published online: 17 Dec 2019

References

  • Wu H, Xiong WC, Mei L. To build a synapse: signaling pathways in neuromuscular junction assembly. Dev Camb Engl. 2010;137:1017–1033.
  • Punga AR, Ruegg MA. Signaling and aging at the neuromuscular synapse: lessons learnt from neuromuscular diseases. Curr Opin Pharmacol. 2012;12:340–346.
  • Cifuentes-Diaz C, Nicole S, Velasco ME, et al. Neurofilament accumulation at the motor endplate and lack of axonal sprouting in a spinal muscular atrophy mouse model. Hum Mol Genet. 2002;11:1439–1447.
  • Kariya S, Park G-H, Maeno-Hikichi Y, et al. Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum Mol Genet. 2008;17:2552–2569.
  • Kong L, Wang X, Choe DW, et al. Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice. J Neurosci Off J Soc Neurosci. 2009;29:842–851.
  • Moloney EB, de Winter F, Verhaagen J. ALS as a distal axonopathy: molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease. Front Neurosci. 2014;8:252.
  • Murray LM, Talbot K, Gillingwater TH. Review: neuromuscular synaptic vulnerability in motor neurone disease: amyotrophic lateral sclerosis and spinal muscular atrophy. Neuropathol Appl Neurobiol. 2010;36:133–156.
  • Gonzalez-Freire M, de Cabo R, Studenski SA, et al. The neuromuscular junction: aging at the crossroad between nerves and muscle. Front Aging Neurosci. 2014;6:208.
  • Taetzsch T, Valdez G. NMJ maintenance and repair in aging. Curr Opin Physiol. 2018;4:57–64.
  • Webster RG. Animal models of the neuromuscular junction, vitally informative for understanding function and the molecular mechanisms of congenital myasthenic syndromes. Int J Mol Sci. 2018;19(5):1326.
  • Jones RA, Harrison C, Eaton SL, et al. Cellular and molecular anatomy of the human neuromuscular junction. Cell Rep. 2017;21:2348–2356.
  • Burridge PW, Matsa E, Shukla P, et al. Chemically defined generation of human cardiomyocytes. Nat Methods. 2014;11:855–860.
  • Chunhui X, Shailaja P, Namitha R, et al. Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res. 2002;91:501–508.
  • Jianhua Z, Wilson Gisela F, Soerens Andrew G, et al. Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res. 2009;104:e30–e41.
  • Hay DC, Fletcher J, Payne C, et al. Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling. Proc Natl Acad Sci. 2008;105:12301–12306.
  • Si‐Tayeb K, Noto FK, Nagaoka M, et al. Highly efficient generation of human hepatocyte–like cells from induced pluripotent stem cells. Hepatology. 2010;51:297–305.
  • Guo X, Greene K, Akanda N, et al. In vitro differentiation of functional human skeletal myotubes in a defined system. Biomater Sci. 2014;2:131–138.
  • Rao L, Qian Y, Khodabukus A, et al. Engineering human pluripotent stem cells into a functional skeletal muscle tissue. Nat Commun. 2018;9:1–12.
  • Hu B-Y, Zhang S-C. Differentiation of spinal motor neurons from pluripotent human stem cells. Nat Protoc. 2009;4:1295–1304.
  • Maury Y, Côme J, Piskorowski RA, et al. Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes. Nat Biotechnol. 2015;33:89–96.
  • Du Z-W, Chen H, Liu H, et al. Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells. Nat Commun. 2015;6:1–9.
  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–676.
  • Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–872.
  • Corti S, Nizzardo M, Simone C, et al. Genetic correction of human induced pluripotent stem cells from patients with spinal muscular atrophy. Sci Transl Med. 2012;4:165ra162.
  • Ebert AD, Yu J, Rose FF, et al. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature. 2009;457:277–280.
  • Sareen D, Ebert AD, Heins BM, et al. Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy. PloS One. 2012;7:e39113.
  • Dimos JT, Rodolfa KT, Niakan KK, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 2008;321:1218–1221.
  • Sareen D, O’Rourke JG, Meera P, et al. Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Sci Transl Med. 2013;5:208ra149.
  • Serio A, Bilican B, Barmada SJ, et al. Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy. Proc Natl Acad Sci U S A. 2013;110:4697–4702.
  • Kiskinis E, Sandoe J, Williams LA, et al. Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1. Cell Stem Cell. 2014;14:781–795.
  • Devlin A-C, Burr K, Borooah S, et al. Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability. Nat Commun. 2015;6:1–12.
  • Sances S, Bruijn LI, Chandran S, et al. Modeling ALS with motor neurons derived from human induced pluripotent stem cells. Nat Neurosci. 2016;19:542–553.
  • Peterson ER, Crain SM. Regeneration and innervation in cultures of adult mammalian skeletal muscle coupled with fetal rodent spinal cord. Exp Neurol. 1972;36:136–159.
  • Das M, Rumsey JW, Bhargava N, et al. A defined long-term in vitro tissue engineered model of neuromuscular junctions. Biomaterials. 2010;31:4880–4888.
  • Chipman PH, Zhang Y, Rafuse VF. A stem-cell based bioassay to critically assess the pathology of dysfunctional neuromuscular junctions. PloS One. 2014;9:e91643.
  • Li X-J, Du Z-W, Zarnowska ED, et al. Specification of motoneurons from human embryonic stem cells. Nat Biotechnol. 2005;23:215–221.
  • Guo X, Das M, Rumsey J, et al. Neuromuscular junction formation between human stem-cell-derived motoneurons and rat skeletal muscle in a defined system. Tissue Eng Part C Methods. 2010;16:1347–1355.
  • Guo X, Gonzalez M, Stancescu M, et al. Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system. Biomaterials. 2011;32:9602–9611.
  • Demestre M, Orth M, Föhr KJ, et al. Formation and characterisation of neuromuscular junctions between hiPSC derived motoneurons and myotubes. Stem Cell Res. 2015;15:328–336.
  • Campenot RB. Local control of neurite development by nerve growth factor. Proc Natl Acad Sci U S A. 1977;74:4516–4519.
  • Jia M, Li M, Dunlap V, et al. The thrombin receptor mediates functional activity-dependent neuromuscular synapse reduction via protein kinase C activation in vitro. J Neurobiol. 1999;38:369–381.
  • Nelson PG, Fields RD, Yu C, et al. Synapse elimination from the mouse neuromuscular junction in vitro: a non-hebbian activity-dependent process. J Neurobiol. 1993;24:1517–1530.
  • Southam KA, King AE, Blizzard CA, et al. Microfluidic primary culture model of the lower motor neuron–neuromuscular junction circuit. J Neurosci Methods. 2013;218:164–169.
  • Park HS, Liu S, McDonald J, et al. Neuromuscular junction in a microfluidic device. 2013 35th Annu Int Conf IEEE Eng Med Biol Soc EMBC. 2013;2833–2835.
  • Zahavi EE, Ionescu A, Gluska S, et al. A compartmentalized microfluidic neuromuscular co-culture system reveals spatial aspects of GDNF functions. J Cell Sci. 2015;128:1241–1252.
  • Santhanam N, Kumanchik L, Guo X, et al. Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics. Biomaterials. 2018;166:64–78.
  • Happe CL, Tenerelli KP, Gromova AK, et al. Mechanically patterned neuromuscular junctions-in-a-dish have improved functional maturation. Mol Biol Cell. 2017;28:1950–1958.
  • Luo B, Tian L, Chen N, et al. Electrospun nanofibers facilitate better alignment, differentiation, and long-term culture in an in vitro model of the neuromuscular junction (NMJ). Biomater Sci. 2018;6:3262–3272.
  • Madden L, Juhas M, Kraus WE, et al. Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs. eLife. 2015;4:e04885.
  • Okano T, Matsuda T. Tissue engineered skeletal muscle: preparation of highly dense, highly oriented hybrid muscular tissues. Cell Transplant. 1998;7:71–82.
  • Powell CA, Smiley BL, Mills J, et al. Mechanical stimulation improves tissue-engineered human skeletal muscle. Am J Physiol-Cell Physiol. 2002;283:C1557–C1565.
  • Ronaldson-Bouchard K, Ma SP, Yeager K, et al. Advanced maturation of human cardiac tissue grown from pluripotent stem cells. Nature. 2018;556:239–243.
  • Thavandiran N, Dubois N, Mikryukov A, et al. Design and formulation of functional pluripotent stem cell-derived cardiac microtissues. Proc Natl Acad Sci. 2013;110:E4698–E4707.
  • Morimoto Y, Kato-Negishi M, Onoe H, et al. Three-dimensional neuron-muscle constructs with neuromuscular junctions. Biomaterials. 2013;34:9413–9419.
  • Smith AST, Passey SL, Martin NRW, et al. Creating interactions between tissue-engineered skeletal muscle and the peripheral nervous system. Cells Tissues Organs. 2016;202:143–158.
  • Smith AST, Long CJ, Pirozzi K, et al. A functional system for high-content screening of neuromuscular junctions in vitro. Technology. 2013;1:37–48.
  • Afshar Bakooshli M, Lippmann ES, Mulcahy B, et al. A 3D culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction. eLife. 2019;8:e44530.
  • Boyden ES, Zhang F, Bamberg E, et al. Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci. 2005;8:1263–1268.
  • Steinbeck JA, Jaiswal MK, Calder EL, et al. Functional connectivity under optogenetic control allows modeling of human neuromuscular disease. Cell Stem Cell. 2016;18:134–143.
  • Uzel SGM, Platt RJ, Subramanian V, et al. Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units. Sci Adv. 2016;2:e1501429.
  • Osaki T, Uzel SGM, Kamm RD. Microphysiological 3D model of amyotrophic lateral sclerosis (ALS) from human iPS-derived muscle cells and optogenetic motor neurons. Sci Adv. 2018;4:eaat5847.
  • Vila OF, Uzel SGM, Ma SP, et al. Quantification of human neuromuscular function through optogenetics. Theranostics. 2019;9:1232–1246.
  • Kusner LL, Kaminski HJ, Soltys J. Effect of complement and its regulation on myasthenia gravis pathogenesis. Expert Rev Clin Immunol. 2008;4:43–52.
  • Carr AS, Cardwell CR, McCarron PO, et al. A systematic review of population based epidemiological studies in myasthenia gravis. BMC Neurol. 2010;10:46.
  • Yoshida M, Kitaoka S, Egawa N, et al. Modeling the early phenotype at the neuromuscular junction of spinal muscular atrophy using patient-derived iPSCs. Stem Cell Rep. 2015;4:561–568.
  • Blasco H, Mavel S, Corcia P, et al. The glutamate hypothesis in ALS: pathophysiology and drug development. Current Medicinal Chemistry. 2014;21(31):3551–3575.
  • Plaitakis A. Glutamate dysfunction and selective motor neuron degeneration in amyotrophic lateral sclerosis: a hypothesis. Ann Neurol. 1990;28:3–8.
  • Charoensook SN, Williams DJ, Chakraborty S, et al. Bioreactor model of neuromuscular junction with electrical stimulation for pharmacological potency testing. Integr Biol Quant Biosci Nano Macro. 2017;9:956–967.
  • Macia E, Ehrlich M, Massol R, et al. Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell. 2006;10:839–850.
  • Dressler D, Saberi FA. Botulinum toxin: mechanisms of action. Eur Neurol. 2005;53:3–9.
  • Huber A, France RM, Riccalton-Banks L, et al. The intercostal NMJ assay: a new alternative to the conventional LD50 assay for the determination of the therapeutic potency of botulinum toxin preparations. Altern Lab Anim ATLA. 2008;36:141–152.
  • Blount P, Merlie JP. Molecular basis of the two nonequivalent ligand binding sites of the muscle nicotinic acetylcholine receptor. Neuron. 1989;3:349–357.
  • Sine SM. Molecular dissection of subunit interfaces in the acetylcholine receptor: identification of residues that determine curare selectivity. Proc Natl Acad Sci U S A. 1993;90:9436–9440.
  • Chang CC, Lee CY. Isolation of neurotoxins from the venom of bungarus multicinctus and their modes of neuromuscular blocking action. Arch Int Pharmacodyn Ther. 1963;144:241–257.
  • McArdle JJ, Lentz TL, Witzemann V, et al. Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptor. J Pharmacol Exp Ther. 1999;289:543–550.
  • Rapamycin Treatment for ALS. Full Text View - ClinicalTrials.gov. [cited 2019 Sep 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT03359538.
  • Mandrioli J, D’Amico R, Zucchi E, et al. Rapamycin treatment for amyotrophic lateral sclerosis: protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial). Medicine (Baltimore). 2018;97:e11119.
  • Phase 1 dose escalation study of bosutinib in patients with Amyotrophic Lateral Sclerosis (ALS). [cited 2019 Sep 12]. Available from: https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2051190001.
  • Mars T, Yu KJ, Tang XM, et al. Differentiation of glial cells and motor neurons during the formation of neuromuscular junctions in cocultures of rat spinal cord explant and human muscle. J Comp Neurol. 2001;438:239–251.
  • Piccini JP, Whellan DJ, Berridge BR, et al. Current challenges in the evaluation of cardiac safety during drug development: translational medicine meets the critical path initiative. Am Heart J. 2009;158:317–326.
  • Boos JA, Misun PM, Michlmayr A, et al. Microfluidic multitissue platform for advanced embryotoxicity testing In Vitro. Adv Sci. 2019;6:1900294.
  • Kimura H, Sakai Y, Fujii T. Organ/body-on-a-chip based on microfluidic technology for drug discovery. Drug Metab Pharmacokinet. 2018;33:43–48.

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