{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:27:44Z","timestamp":1779114464306,"version":"3.51.4"},"reference-count":84,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100008431","name":"Consejer\u00eda de Educaci\u00f3n, Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["SA030P17"],"award-info":[{"award-number":["SA030P17"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008431","name":"Consejer\u00eda de Educaci\u00f3n, Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["SA112P24"],"award-info":[{"award-number":["SA112P24"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008431","name":"Consejer\u00eda de Educaci\u00f3n, Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["SA129P20"],"award-info":[{"award-number":["SA129P20"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014064","name":"Universidad de Salamanca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014064","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2019-106943RB-I00"],"award-info":[{"award-number":["PID2019-106943RB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2022-140456NB-I00"],"award-info":[{"award-number":["PID2022-140456NB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2016-79668-R"],"award-info":[{"award-number":["SAF2016-79668-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023432","name":"Centro en Red de Medicina Regenerativa y Terapia celular de Castilla y Le\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023432","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Tissue Eng"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>Cell therapy is a promising strategy for tackling neurodegenerative diseases. The most outstanding results with this approach usually involve neuroprotection of damaged neurons at risk of death, but only with limited success. Current therapies are often based on the idea of \u201cone gene, one disease, one drug\u201d for single targets, a concept that limits their actual effectiveness. In contrast, combining different strategies can establish an advanced cell therapy that can slow down neuronal degeneration. In this study, we took advantage of the combination of cell and gene therapy, by transplanting bone marrow stem cells genetically modified to overexpress insulin-like growth factor 1 (IGF1) into a model of selective neurodegeneration, the PCD mouse. This animal is characterized by progressive neuronal loss in the olfactory bulb and alterations in IGF1 levels, among other symptoms. Using different techniques (cell cultures, viral transduction, cell transplants, flow cytometry, qPCR, ELISA, immunohistochemistry, advanced image analysis), our findings showed that neuronal death was virtually blocked, even 130\u2009days after cell transplantation, a result clearly more successful than previous studies. The effects of this transplant are based in part on the regulation of neuroinflammation, increasing the proportion of reactive microglia and reducing that of proinflammatory microglia. In addition, IGF1 overexpression dramatically reduced DNA damage in mutant animals via IGF binding protein 3 pathway: this enhances neuroprotection by complementing the basal effect of cell therapy itself. In summary, our work supports the idea that combining therapeutic approaches and their synergies is a more effective tactic for combating neuronal loss.<\/jats:p>","DOI":"10.1177\/20417314261442787","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T13:21:26Z","timestamp":1778937686000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetically modified bone marrow cells halt mitral cell loss by modulating inflammation and protecting against DNA damage"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3705-817X","authenticated-orcid":false,"given":"David","family":"D\u00edaz","sequence":"first","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute for Neuroscience of Castilla y Le\u00f3n (INCyL), Universidad de Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva Mar\u00eda","family":"Baranda-Alonso","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute for Neuroscience of Castilla y Le\u00f3n (INCyL), Universidad de Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"P\u00e9rez-Revuelta","sequence":"additional","affiliation":[{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Felipe","family":"Zapata-Acevedo","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Neurociencias (NeURos), Centro de Neurociencias Neurovitae-UR, Instituto de Medicina Traslacional (IMT), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogot\u00e1, Colombia"},{"name":"Laboratorio de Neurofisiolog\u00eda Celular, Grupo de Neurociencia Traslacional, Facultad de Medicina, Universidad de los Andes, Bogot\u00e1, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Torossian","sequence":"additional","affiliation":[{"name":"INSERM UMRS-MD 1197, Universit\u00e9 Paris-Saclay, H\u00f4pital Paul Brousse, Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrienne","family":"Anginot","sequence":"additional","affiliation":[{"name":"INSERM UMRS-MD 1197, Universit\u00e9 Paris-Saclay, H\u00f4pital Paul Brousse, Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Ram\u00f3n","family":"Alonso","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute for Neuroscience of Castilla y Le\u00f3n (INCyL), Universidad de Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Caroline","family":"Le Bousse-Kerdil\u00e8s","sequence":"additional","affiliation":[{"name":"INSERM UMRS-MD 1197, Universit\u00e9 Paris-Saclay, H\u00f4pital Paul Brousse, Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Weruaga","sequence":"additional","affiliation":[{"name":"Laboratory of Neuronal Plasticity and Neurorepair, Institute for Neuroscience of Castilla y Le\u00f3n (INCyL), Universidad de Salamanca, Spain"},{"name":"Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26026"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22042153"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S395010"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.1.208"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.07.065"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(82)90206-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20352"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2006.08.002"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22431"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2025.106248"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0260-12.2012"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368912X638900"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/term.2626"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/term.2925"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368910X552826"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.10.002"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104896"},{"key":"e_1_3_3_19_2","doi-asserted-by":"crossref","unstructured":"Calvo PM Hern\u00e1ndez RG Pastor AM et al. VEGF and Neuronal Survival. Neuroscientist 2024; 30(1): 71-86.","DOI":"10.1177\/10738584221120803"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn812"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15021719"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1630191"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(03)00562-3"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-15-05678.2001"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.10.082"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05970-1"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.773696"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2020.108307"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2016.00159"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.671247"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25978"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1120836"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.3791\/60822"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20120146"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-0556-2-6"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab104"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1177\/1073858414547538"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00328-2"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-018-0250-4"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07295-7"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1720"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2002.8004"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1775"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1779"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0470-3"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-01821-4"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2014.10.002"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26020538"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(96)00168-X"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02324-x"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0298-5"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.06.015"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01044-3"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)01715-3"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1833-z"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25207"},{"issue":"1","key":"e_1_3_3_57_2","article-title":"Lobe X of the cerebellum: a natural neuro-resistant region","volume":"2","author":"Hern\u00e1ndez-P\u00e9rez C","year":"2023","unstructured":"Hern\u00e1ndez-P\u00e9rez C, Weruaga E, D\u00edaz D. Lobe X of the cerebellum: a natural neuro-resistant region. Anat 2023; 2(1): 43-62.","journal-title":"Anat"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms262110378"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27031145"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490410517"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0212-1"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2017.12.019"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e13777"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0203-5"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4397"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-020-00221-2"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119691"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-051116-052358"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12011"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.207"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20663"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00084"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4222"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.997786"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.246041"},{"issue":"6","key":"e_1_3_3_76_2","article-title":"Mature neurons: equipped for survival","volume":"4","author":"Kole AJ","year":"2013","unstructured":"Kole AJ, Annis RP, Deshmukh M. Mature neurons: equipped for survival. Cell Death Discov 2013; 4(6): e689.","journal-title":"Cell Death Discov"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2014.1802"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052484"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2012.03.009"},{"key":"e_1_3_3_80_2","first-page":"1","article-title":"The impact of the IGF-1 system of cancer cells on radiation response - an in vitro study","volume":"7","author":"Venkatachalam S","year":"2017","unstructured":"Venkatachalam S, Mettler E, Fottner C, et al. The impact of the IGF-1 system of cancer cells on radiation response - an in vitro study. Clin Transl Radiat Oncol 2017; 7: 1\u20138.","journal-title":"Clin Transl Radiat Oncol"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-0047"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00045"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-3-15"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1139\/y05-041"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"}],"container-title":["Journal of Tissue Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20417314261442787","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20417314261442787","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20417314261442787","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T13:16:27Z","timestamp":1779110187000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20417314261442787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":84,"alternative-id":["10.1177\/20417314261442787"],"URL":"https:\/\/doi.org\/10.1177\/20417314261442787","relation":{},"ISSN":["2041-7314","2041-7314"],"issn-type":[{"value":"2041-7314","type":"print"},{"value":"2041-7314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"article-number":"20417314261442787"}}