{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:01:51Z","timestamp":1792789311730,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia\/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia\/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf, increased expression of anti-inflammatory cytokine genes (Il4, Il10, Il13) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells.<\/jats:p>","DOI":"10.3390\/ijms22094694","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T01:43:24Z","timestamp":1619660604000},"page":"4694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Therapeutic Effects of hiPSC-Derived Glial and Neuronal Progenitor Cells-Conditioned Medium in Experimental Ischemic Stroke in Rats"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7842-7635","authenticated-orcid":false,"given":"Diana","family":"Salikhova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"},{"name":"Research Institute of Human Morphology, 117418 Moscow, 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hypoxia models","volume":"15","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fcell.2015.00002","article-title":"Induced pluripotent stem cells: Applications in regenerative medicine, disease modeling, and drug discovery","volume":"3","author":"Singh","year":"2015","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-1-4939-3584-0_7","article-title":"Paracrine mechanisms of mesenchymal stem cells in tissue repair","volume":"1416","author":"Gnecchi","year":"2016","journal-title":"Mesenchymal Stem Cells"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2217\/rme.09.74","article-title":"Stem cell paracrine actions and tissue regeneration","volume":"5","author":"Baraniak","year":"2010","journal-title":"Regen. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2019.04.002","article-title":"The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine","volume":"46","author":"Kumar","year":"2019","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.jcyt.2013.07.017","article-title":"Paracrine mechanisms of proliferative, anti-apoptotic and anti-inflammatory effects of mesenchymal stromal cells in models ofacute organ injury","volume":"16","author":"Khubutiya","year":"2014","journal-title":"Cytotherapy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jchemneu.2019.02.003","article-title":"Conditioned medium obtained from mesenchymal stem cells attenuates focal cerebral ischemia reperfusion injury through activation of ERK1\/ERK2-BDNF signaling pathway","volume":"97","author":"Aboutaleb","year":"2019","journal-title":"J. Chem. Neuroanat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/965849","article-title":"Prospect of Stem Cell Conditioned Medium in Regenerative Medicine","volume":"2014","author":"Pawitan","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1423-0127-21-5","article-title":"Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats","volume":"21","author":"Tsai","year":"2014","journal-title":"J. Biomed. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/nature22067","article-title":"Human umbilical cord plasma proteins revitalize hippocampal function in aged mice","volume":"544","author":"Castellano","year":"2017","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s11745-002-0981-4","article-title":"Apolipoproteins A-I and A-II downregulate neutrophil functions","volume":"37","author":"Furlaneto","year":"2002","journal-title":"Lipids"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.cytogfr.2008.08.001","article-title":"Osteopontin: Role in immune regulation and stress responses","volume":"19","author":"Wang","year":"2008","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1161\/STROKEAHA.110.599118","article-title":"Osteopontin reduced hypoxia-ischemia neonatal brain injury by suppression of apoptosis in a rat pup model","volume":"42","author":"Chen","year":"2011","journal-title":"Stroke"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.biomaterials.2016.03.048","article-title":"Glypican-1 nanoliposomes for potentiating growth factor activity in therapeutic angiogenesis","volume":"94","author":"Monteforte","year":"2016","journal-title":"Biomaterials"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nm1233","article-title":"Lactadherin promotes VEGF-dependent neovascularization","volume":"11","author":"Silvestre","year":"2005","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s12192-013-0439-6","article-title":"Hsp70 regulation on Nox4\/p22phox and cytoskeletal integrity as an effect of losartan in vascular smooth muscle cells","volume":"19","author":"Bocanegra","year":"2014","journal-title":"Cell Stress Chaperones"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1002\/jnr.21919","article-title":"Leukemia inhibitory factor promotes olfactory sensory neuronal survival via phosphoinositide 3-kinase pathway activation and Bcl-2","volume":"87","author":"Moon","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.brainres.2013.01.017","article-title":"Gremlin is a novel VTA derived neuroprotective factor for dopamine neurons","volume":"1500","author":"Phani","year":"2013","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8597","DOI":"10.1523\/JNEUROSCI.20-23-08597.2000","article-title":"Growth\/differentiation factor-15\/macrophage inhibitory cytokine-1 is a novel trophic factor for midbrain dopaminergic neurons in vivo","volume":"20","author":"Strelau","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2788","DOI":"10.1016\/j.febslet.2005.04.011","article-title":"NMR structure and regulated expression in APL cell of human SH3BGRL3","volume":"579","author":"Xu","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nm.3778","article-title":"Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction","volume":"21","author":"Reboll","year":"2015","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40902-017-0106-4","article-title":"Angiogenesis in newly regenerated bone by secretomes of human mesenchymal stem cells","volume":"39","author":"Katagiri","year":"2017","journal-title":"Maxillofac. Plast. Reconstr. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2040-7378-2-13","article-title":"Functional assessments in the rodent stroke model","volume":"2","author":"Schaar","year":"2010","journal-title":"Exp. Transl. Stroke Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1139\/apnm-2016-0651","article-title":"Ellagic acid protects against neuron damage in ischemic stroke through regulating the ratio of Bcl-2\/Bax expression","volume":"42","author":"Liu","year":"2017","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1002\/sctm.18-0009","article-title":"Secretome of Undifferentiated Neural Progenitor Cells Induces Histological and Motor Improvements in a Rat Model of Parkinson\u2019s Disease","volume":"7","author":"Teixeira","year":"2018","journal-title":"Stem Cells Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/14789450.2020.1745069","article-title":"Proteomic examination of the neuroglial secretome: Lessons for the clinic","volume":"17","author":"Kim","year":"2020","journal-title":"Expert Rev. Proteom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/pmic.201300236","article-title":"Proteome of brain glia: The molecular basis of diverse glial phenotypes","volume":"14","author":"Jha","year":"2014","journal-title":"Proteomics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1586\/epr.10.6","article-title":"Combined analysis of the glia secretome and the CSF proteome: Neuroinflammation and novel biomarkers","volume":"7","author":"Suk","year":"2010","journal-title":"Expert Rev. Proteom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1074\/mcp.M500040-MCP200","article-title":"Difference in mass analysis using labeled lysines (DIMAL-K): A new, efficient proteomic quantification method applied to the analysis of astrocytic secretomes","volume":"4","author":"Delcourt","year":"2005","journal-title":"Mol. Cell. Proteom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1002\/pmic.201300495","article-title":"Proteomic analysis of mouse astrocytes and their secretome by a combination of FASP and StageTip-based, high pH, reversed-phase fractionation","volume":"14","author":"Han","year":"2014","journal-title":"Proteomics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"239","DOI":"10.15252\/embj.201592705","article-title":"Astrocytes as secretory cells of the central nervous system: Idiosyncrasies of vesicular secretion","volume":"35","author":"Verkhratsky","year":"2016","journal-title":"EMBO J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainres.2006.07.120","article-title":"The role of TNF-alpha and its receptors in the production of NGF and GDNF by astrocytes","volume":"1116","author":"Kuno","year":"2006","journal-title":"Brain Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1017\/S1740925X05000013","article-title":"Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes","volume":"1","author":"Gozes","year":"2004","journal-title":"Neuron Glia Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.pneurobio.2017.12.003","article-title":"Functional dissection of astrocyte-secreted proteins: Implications in brain health and diseases","volume":"162","author":"Jha","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_35","first-page":"1","article-title":"Neural stem cell-conditioned medium ameliorated cerebral ischemia-reperfusion injury in rats","volume":"2018","author":"Yang","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.3727\/096368912X657936","article-title":"In Vivo and In Vitro Characterization of the Angiogenic Effect of CTX0E03 Human Neural Stem Cells","volume":"22","author":"Hicks","year":"2013","journal-title":"Cell Transpl."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.steroids.2007.02.003","article-title":"Neurotrophic and neuroprotective actions of estrogen: Basic mechanisms and clinical implications","volume":"72","author":"Brann","year":"2007","journal-title":"Steroids"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1089\/scd.2020.0020","article-title":"Human Neural Stem Cell-Conditioned Medium Inhibits Inflammation in Macrophages Via Sirt-1 Signaling Pathway In Vitro and Promotes Sciatic Nerve Injury Recovery in Rats","volume":"29","author":"Chen","year":"2020","journal-title":"Stem Cells Dev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chen, Y.C., Chang, Y.W., Tan, K.P., Shen, Y.S., Wang, Y.H., and Chang, C.H. (2018). Can mesenchymal stem cells and their conditioned medium assist inflammatory chondrocytes recovery?. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205563"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1161\/STROKEAHA.117.018288","article-title":"Intra-Arterial Delivery of Cell Therapies for Stroke","volume":"49","author":"Guzman","year":"2018","journal-title":"Stroke"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/brb3.1214","article-title":"Neural stem cell therapy for stroke: A multimechanistic approach to restoring neurological function","volume":"9","author":"Baker","year":"2019","journal-title":"Brain Behav."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Toyoshima, A., Yasuhara, T., Kameda, M., Morimoto, J., Takeuchi, H., Wang, F., Sasaki, T., Sasada, S., Shinko, A., and Wakamori, T. (2015). Intra-Arterial Transplantation of Allogeneic Mesenchymal Stem Cells Mounts Neuroprotective Effects in a Transient Ischemic Stroke Model in Rats: Analyses of Therapeutic Time Window and Its Mechanisms. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127302"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1177\/0271678X18776802","article-title":"The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke","volume":"38","author":"Cunningham","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_44","first-page":"1","article-title":"Adult Stem Cells and Induced Pluripotent Stem Cells for Stroke Treatment","volume":"10","author":"Castillo","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Merali, Z., Huang, K., Mikulis, D., Silver, F., and Kassner, A. (2017). Evolution of blood-brain-barrier permeability after acute ischemic stroke. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171558"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1007\/s10072-020-04296-7","article-title":"Value of thrombus imaging in predicting the outcomes of patients with large-vessel occlusive strokes after endovascular therapy","volume":"41","author":"Huang","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnins.2021.641970","article-title":"Intra-Arterial Stem Cell Transplantation in Experimental Stroke in Rats: Real-Time MR Visualization of Transplanted Cells Starting With Their First Pass Through the Brain With Regard to the Therapeutic Action","volume":"15","author":"Namestnikova","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nbt.1529","article-title":"Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling","volume":"27","author":"Chambers","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Shutova, M.V., Chestkov, I.V., Bogomazova, A.N., Lagarkova, M.A., and Kiselev, S.L. (2011). Generation of iPS Cells from Human Umbilical Vein Endothelial Cells by Lentiviral Transduction and Their Differentiation to Neuronal Lineage. Hum. Press, 133\u2013149.","DOI":"10.1007\/978-1-61779-267-0_11"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1007\/s00018-011-0770-y","article-title":"Specification of neuronal and glial subtypes from human pluripotent stem cells","volume":"68","author":"Liu","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.stemcr.2017.06.018","article-title":"An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells","volume":"9","author":"Tcw","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1002\/pmic.201000595","article-title":"SearchGUI: An open-source graphical user interface for simultaneous OMSSA and X!Tandem searches","volume":"11","author":"Vaudel","year":"2011","journal-title":"Proteomics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3995\/jstroke.8.1","article-title":"Experimental studies of ischemic brain edema","volume":"8","author":"Koizumi","year":"1986","journal-title":"Jpn. J. Stroke"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1161\/01.STR.20.1.84","article-title":"Reversible middle cerebral artery occlusion without craniectomy in rats","volume":"20","author":"Longa","year":"1989","journal-title":"Stroke"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s12975-017-0590-y","article-title":"MRI Guiding of the Middle Cerebral Artery Occlusion in Rats Aimed to Improve Stroke Modeling","volume":"9","author":"Gubskiy","year":"2018","journal-title":"Transl. Stroke Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4694\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:55:00Z","timestamp":1760162100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,29]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22094694"],"URL":"https:\/\/doi.org\/10.3390\/ijms22094694","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,29]]}}}