{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:38:46Z","timestamp":1787593126153,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RC2020-2021"],"award-info":[{"award-number":["RC2020-2021"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003197","name":"Italian Medicines Agency","doi-asserted-by":"publisher","award":["2016-02364678"],"award-info":[{"award-number":["2016-02364678"]}],"id":[{"id":"10.13039\/501100003197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007802","name":"Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica","doi-asserted-by":"publisher","award":["MLOpathy"],"award-info":[{"award-number":["MLOpathy"]}],"id":[{"id":"10.13039\/501100007802","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mitochondria alterations are present in tissues derived from patients and animal models, but no data are available for peripheral blood mononuclear cells (PBMCs) of ALS patients. This work aims to investigate mitophagy in PBMCs of sporadic (sALS) patients and how this pathway can be tuned by using small molecules. We found the presence of morphologically atypical mitochondria by TEM and morphological abnormalities by MitoTracker\u2122. We found a decreased number of healthy mitochondria in sALS PBMCs and an impairment of mitophagy with western blot and immunofluorescence. After rapamycin treatment, we found a higher increase in the LC3 marker in sALS PBMCs, while after NH4Cl treatment, we found a lower increase in the LC3 marker. Finally, mTOR-independent autophagy induction with trehalose resulted in a significant decrease in the lysosomes level sALS PBMCs. Our data suggest that the presence of morphologically altered mitochondria and an inefficient turnover of damaged mitochondria in PBMCs of sALS patients rely on the impairment of the mitophagy pathway. We also found that the induction of the mTOR-independent autophagy pathway leads to a decrease in lysosomes level, suggesting a more sensitivity of sALS PBMCs to trehalose. Such evidence suggests that trehalose could represent an effective treatment for ALS patients.<\/jats:p>","DOI":"10.3390\/cells11081272","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T05:13:08Z","timestamp":1649481188000},"page":"1272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Lysosomes Dysfunction Causes Mitophagy Impairment in PBMCs of Sporadic ALS Patients"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9461-756X","authenticated-orcid":false,"given":"Matteo","family":"Bordoni","sequence":"first","affiliation":[{"name":"Genomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3041-0612","authenticated-orcid":false,"given":"Orietta","family":"Pansarasa","sequence":"additional","affiliation":[{"name":"Genomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6703-1755","authenticated-orcid":false,"given":"Eveljn","family":"Scarian","sequence":"additional","affiliation":[{"name":"Genomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-846X","authenticated-orcid":false,"given":"Riccardo","family":"Cristofani","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Universit\u00e0 Degli Studi di Milano, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Leone","sequence":"additional","affiliation":[{"name":"Casa di Cura Ars Medica S.p.a, 00191 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1244-4453","authenticated-orcid":false,"given":"Valentina","family":"Fantini","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Neurogenetic, Golgi-Cenci Foundation, 20081 Abbiategrasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8668-3855","authenticated-orcid":false,"given":"Maria","family":"Garofalo","sequence":"additional","affiliation":[{"name":"Genomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Diamanti","sequence":"additional","affiliation":[{"name":"Neuroncology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Bernuzzi","sequence":"additional","affiliation":[{"name":"Immunohematological and Transfusional Service and Centre of Transplantation Immunology, IRCCS \u201cSan Matteo Foundation\u201d, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6589-6907","authenticated-orcid":false,"given":"Stella","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Genomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4603-396X","authenticated-orcid":false,"given":"Stephana","family":"Carelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences \u201cL. Sacco\u201d, University of Milan, 20157 Milan, Italy"},{"name":"Pediatric Clinical Research Centre Fondazione \u201cRomeo ed Enrica Invernizzi\u201d, University of Milano, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-0468","authenticated-orcid":false,"given":"Angelo","family":"Poletti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Dipartimento di Eccellenza 2018-2022, Universit\u00e0 Degli Studi di Milano, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9571-0862","authenticated-orcid":false,"given":"Cristina","family":"Cereda","sequence":"additional","affiliation":[{"name":"Genomic and Post-Genomic Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3389\/fnins.2019.00175","article-title":"Psychiatric Symptoms in Amyotrophic Lateral Sclerosis: Beyond a Motor Neuron Disorder","volume":"13","author":"Zucchi","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17071","DOI":"10.1038\/nrdp.2017.71","article-title":"Amyotrophic lateral sclerosis","volume":"3","author":"Hardiman","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1056\/NEJMra1603471","article-title":"Amyotrophic Lateral Sclerosis","volume":"377","author":"Brown","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4103\/1673-5374.200794","article-title":"Current view and perspectives in amyotrophic lateral sclerosis","volume":"12","author":"Mathis","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"132933","DOI":"10.1016\/j.neulet.2017.06.052","article-title":"The role of mitochondria in amyotrophic lateral sclerosis","volume":"710","author":"Smith","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13024-017-0232-6","article-title":"Is amyotrophic lateral sclerosis\/frontotemporal dementia an autophagy disease?","volume":"12","author":"Deng","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.bbrc.2016.07.055","article-title":"Pathways to mitochondrial dysfunction in ALS pathogenesis","volume":"483","author":"Cozzolino","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1152\/physrev.2000.80.1.315","article-title":"Mitochondria and Neuronal Survival","volume":"80","author":"Nicholls","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.neuron.2006.09.018","article-title":"ALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors","volume":"52","author":"Velde","year":"2006","journal-title":"Neuron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/01913120252934260","article-title":"Ultrastructural Changes of Mitochondria in the Skeletal Muscle of Patients with Amyotrophic Lateral Sclerosis","volume":"26","author":"Chung","year":"2002","journal-title":"Ultrastruct. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/nen.0b013e31802c396b","article-title":"Mitochondrial Alterations in the Spinal Cord of Patients with Sporadic Amyotrophic Lateral Sclerosis","volume":"66","author":"Sasaki","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Westrate, L.M., Drocco, J.A., Martin, K.R., Hlavacek, W.S., and MacKeigan, J.P. (2014). Mitochondrial Morphological Features Are Associated with Fission and Fusion Events. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095265"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1146\/annurev-genet-110410-132529","article-title":"Fusion and Fission: Interlinked Processes Critical for Mitochondrial Health","volume":"46","author":"Chan","year":"2012","journal-title":"Annu. Rev. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.nbd.2012.07.004","article-title":"Mutant SOD1G93A triggers mitochondrial fragmentation in spinal cord motor neurons: Neuroprotection by SIRT3 and PGC-1\u03b1","volume":"51","author":"Song","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1093\/hmg\/ddt319","article-title":"The ALS disease-associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons","volume":"22","author":"Wang","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"300","DOI":"10.15252\/embr.201541486","article-title":"The ubiquitin signal and autophagy: An orchestrated dance leading to mitochondrial degradation","volume":"17","author":"Yamano","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105240","DOI":"10.1016\/j.phrs.2020.105240","article-title":"Molecular mechanisms of mitophagy and its roles in neurodegenerative diseases","volume":"163","author":"Li","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13041-017-0287-x","article-title":"TBK1: A new player in ALS linking autophagy and neuroinflammation","volume":"10","author":"Oakes","year":"2017","journal-title":"Mol. Brain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.neuron.2015.06.026","article-title":"Endolysosomal Deficits Augment Mitochondria Pathology in Spinal Motor Neurons of Asymptomatic fALS Mice","volume":"87","author":"Xie","year":"2015","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3389\/fneur.2022.841394","article-title":"The Role of VCP Mutations in the Spectrum of Amyotrophic Lateral Sclerosis\u2014Frontotemporal Dementia","volume":"13","author":"Scarian","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pansarasa, O., Garofalo, M., Scarian, E., Dragoni, F., Garau, J., Di Gerlando, R., Diamanti, L., Bordoni, M., and Gagliardi, S. (2022). Biomarkers in Human Peripheral Blood Mononuclear Cells: The State of the Art in Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052580"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bordoni, M., Pansarasa, O., Dell\u2019Orco, M., Crippa, V., Gagliardi, S., Sproviero, D., Bernuzzi, S., Diamanti, L., Ceroni, M., and Tedeschi, G. (2019). Nuclear Phospho-SOD1 Protects DNA from Oxidative Stress Damage in Amyotrophic Lateral Sclerosis. J. Clin. Med., 8.","DOI":"10.3390\/jcm8050729"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Cereda, C., Leoni, E., Milani, P., Pansarasa, O., Mazzini, G., Guareschi, S., Alvisi, E., Ghiroldi, A., Diamanti, L., and Bernuzzi, S. (2013). Altered Intracellular Localization of SOD1 in Leukocytes from Patients with Sporadic Amyotrophic Lateral Sclerosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075916"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1038\/s41598-018-20679-5","article-title":"Long non-coding and coding RNAs characterization in Peripheral Blood Mononuclear Cells and Spinal Cord from Amyotrophic Lateral Sclerosis patients","volume":"8","author":"Gagliardi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3109\/21678421.2015.1049183","article-title":"A revision of the El Escorial criteria\u20142015","volume":"16","author":"Ludolph","year":"2015","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e9716","DOI":"10.1371\/journal.pone.0009716","article-title":"In Vivo Accumulation of Helicobacter pylori Products, NOD1, Ubiquitinated Proteins and Proteasome in a Novel Cytoplasmic Structure","volume":"5","author":"Necchi","year":"2010","journal-title":"PLoS ONE"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1073\/pnas.1115402109","article-title":"An over-oxidized form of superoxide dismutase found in sporadic amyotrophic lateral sclerosis with bulbar onset shares a toxic mechanism with mutant SOD1","volume":"109","author":"Guareschi","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","first-page":"1890","article-title":"Mitochondrial fusion and fission proteins: Novel therapeutic targets for combating cardiovascular disease","volume":"171","author":"Hall","year":"2014","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00018-017-2603-0","article-title":"The ever-growing complexity of the mitochondrial fission machinery","volume":"75","author":"Pagliuso","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_30","first-page":"2313","article-title":"Impaired OMA1-dependent cleavage of OPA1 and reduced DRP1 fission activity combine to prevent mitophagy in cells that are dependent on oxidative phosphorylation","volume":"127","author":"MacVicar","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rottenberg, H., and Hoek, J. (2021). The Mitochondrial Permeability Transition: Nexus of Aging, Disease and Longevity. Cells, 10.","DOI":"10.3390\/cells10010079"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.neuint.2017.02.007","article-title":"Mitophagy in neurodegeneration and aging","volume":"109","author":"Fivenson","year":"2017","journal-title":"Neurochem. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.4161\/auto.28615","article-title":"BECN1 is involved in the initiation of mitophagy: It facilitates PARK2 translocation to mitochondria","volume":"10","author":"Choubey","year":"2014","journal-title":"Autophagy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10059-011-0034-6","article-title":"Targeting the autophagy pathway using ectopic expression of Beclin 1 in combination with rapamycin in drug-resistant v-Ha-ras-transformed NIH 3T3 cells","volume":"31","author":"Eum","year":"2011","journal-title":"Mol. Cells"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1159\/000323984","article-title":"Induction of metabolic acidosis with ammonium chloride (NH4Cl) in mice and rats--species differences and technical considerations","volume":"26","author":"Nowik","year":"2010","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"dmm031625","DOI":"10.1242\/dmm.031625","article-title":"Lymphoblastoid cell lines as a model to understand amyotrophic lateral sclerosis disease mechanisms","volume":"11","author":"Pansarasa","year":"2018","journal-title":"Dis. Models Mech."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/0896-6273(95)90259-7","article-title":"An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria","volume":"14","author":"Wong","year":"1995","journal-title":"Neuron"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hadano, S., Otomo, A., Kunita, R., Suzuki-Utsunomiya, K., Akatsuka, A., Koike, M., Aoki, M., Uchiyama, Y., Itoyama, Y., and Ikeda, J.E. (2010). Loss of ALS2\/Alsin exacerbates motor dysfunction in a SOD1-expressing mouse ALS model by disturbing endolysosomal trafficking. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009805"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1093\/hmg\/ddt528","article-title":"Abnormal mitochondrial transport and morphology are common pathological denominators in SOD1 and TDP43 ALS mouse models","volume":"23","author":"Cortez","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"290","DOI":"10.4161\/auto.5524","article-title":"Altered macroautophagy in the spinal cord of SOD1 mutant mice","volume":"4","author":"Li","year":"2008","journal-title":"Autophagy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/NEN.0b013e3182160690","article-title":"Autophagy in Spinal Cord Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis","volume":"70","author":"Sasaki","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.neuint.2017.08.004","article-title":"Mitophagy in neurodegenerative diseases","volume":"117","author":"Rodolfo","year":"2018","journal-title":"Neurochem. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ceb.2015.01.002","article-title":"PINK1\/Parkin-mediated mitophagy in mammalian cells","volume":"33","author":"Eiyama","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Mugume, Y., Kazibwe, Z., and Bassham, D. (2020). Target of Rapamycin in Control of Autophagy: Puppet Master and Signal Integrator. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218259"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e13171","DOI":"10.1111\/acel.13171","article-title":"Autophagy regulates the localization and degradation of p16 INK4a","volume":"19","author":"Coryell","year":"2020","journal-title":"Aging Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6524","DOI":"10.1002\/jcp.26583","article-title":"Autophagy induction by trehalose: Molecular mechanisms and therapeutic impacts","volume":"233","author":"Caraglia","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1080\/15548627.2018.1535292","article-title":"Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration","volume":"15","author":"Rusmini","year":"2018","journal-title":"Autophagy"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/8\/1272\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:50:52Z","timestamp":1760136652000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/8\/1272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,9]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["cells11081272"],"URL":"https:\/\/doi.org\/10.3390\/cells11081272","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,9]]}}}