{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T06:10:27Z","timestamp":1771827027413,"version":"3.50.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Multiple system atrophy (MSA) is an adult-onset, fatal neurodegenerative disease, classified as a synucleinopathy along with Parkinson\u2019s disease and dementia with Lewy bodies. The etiology of MSA is unknown and the treatment remains symptomatic with limited efficacy. To date most studies have been conducted on genetic mice models, engineered to overexpress \u03b1-synuclein (aSyn); and transmission mice models, treated with intracerebral injections of MSA brain extracts or fibrillar aSyn which can be assembled\n                      <jats:italic>de novo<\/jats:italic>\n                      or using MSA seeds. An\n                      <jats:italic>in vitro<\/jats:italic>\n                      human model is urgently needed to identify the human-specific and even patient-specific molecular mechanisms underlying the disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>For this purpose, we report the generation of six fully characterized induced pluripotent stem cells (iPSCs) lines, which were reprogrammed from disease-derived skin fibroblasts and represent the two major clinical MSA variants with either predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). Five of these cases received postmortem neuropathological confirmation of definite MSA diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The generated iPSC clones meet the International Society for Stem Cell Research (ISSCR) quality standards for genomic stability and functional pluripotency to ensure experimental reproducibility. None of the clones acquired genetic abnormalities after the reprogramming and the extended culture passage, as evaluated by G-banded karyotyping and digital PCR targeting recurrent iPSC copy number variant hotspots. All the clones expressed pluripotent markers as NANOG, LIN28A and SSEA4 and differentiated efficiently into each of the three embryonic germ layers. Furthermore, we assessed their potential for disease modeling by generating oligodendrocytes (OLs), since the pathologic hallmark of MSA is the aberrant accumulation of aSyn within OLs cytoplasm. We obtained both O4+ oligodendrocyte progenitor cells and MBP+ mature oligodendrocyte cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We have created a robust and valuable iPSC collection aimed at correlating the\n                      <jats:italic>in vivo<\/jats:italic>\n                      confirmed clinical and pathological variants with the\n                      <jats:italic>in vitro<\/jats:italic>\n                      phenotypes. This unique tool can contribute to the understanding of MSA pathophysiology, the discovery of therapeutic targets, and the development of therapeutic screening approaches.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1641981","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T05:27:42Z","timestamp":1771824462000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Generation and characterization of human induced pluripotent stem cells from neuropathologically confirmed multiple system atrophy patient-derived fibroblasts"],"prefix":"10.3389","volume":"17","author":[{"given":"Mireia","family":"Alemany-Ribes","sequence":"first","affiliation":[{"name":"Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology","place":["Catalonia, 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Unit and Lab of Parkinson & Other Neurodegenerative Movement Disorders, Hospital Cl\u00ednic\/IDIBAPS\/CIBERNED\/European Reference Network for Rare Neurological Diseases (ERN-RND)\/Institut de Neurocie\u0300ncies \"UBNeuro\", University of Barcelona","place":["Catalonia, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"Fernandez-Santiago","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease & Movement Disorders Unit and Lab of Parkinson & Other Neurodegenerative Movement Disorders, Hospital Cl\u00ednic\/IDIBAPS\/CIBERNED\/European Reference Network for Rare Neurological Diseases (ERN-RND)\/Institut de Neurocie\u0300ncies \"UBNeuro\", University of Barcelona","place":["Catalonia, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manel","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease & Movement Disorders Unit and Lab of Parkinson & Other Neurodegenerative Movement Disorders, Hospital Cl\u00ednic\/IDIBAPS\/CIBERNED\/European Reference Network for Rare Neurological Diseases (ERN-RND)\/Institut de Neurocie\u0300ncies \"UBNeuro\", University of Barcelona","place":["Catalonia, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria J.","family":"Mart\u00ed","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease & Movement Disorders Unit and Lab of Parkinson & Other Neurodegenerative Movement Disorders, Hospital Cl\u00ednic\/IDIBAPS\/CIBERNED\/European Reference Network for Rare Neurological Diseases (ERN-RND)\/Institut de Neurocie\u0300ncies \"UBNeuro\", University of Barcelona","place":["Catalonia, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veerle","family":"Baekelandt","sequence":"additional","affiliation":[{"name":"Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven Brain Institute","place":["KU Leuven, Leuven, Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wouter","family":"Peelaerts","sequence":"additional","affiliation":[{"name":"Laboratory for Advanced Disease Models, Targeted Drug Development and Gene Therapy (ADVANTAGE), Department of Pharmaceutical Sciences","place":["KU Leuven, Leuven, Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Melki","sequence":"additional","affiliation":[{"name":"Institut Fran\u00e7ois Jacob (MIRCen), CEA, and Laboratory of Neurodegenerative Diseases, CNRS","place":["Fontenay-aux-Roses, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaroslau","family":"Compta","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Disease & Movement Disorders Unit and Lab of Parkinson & Other Neurodegenerative Movement Disorders, Hospital Cl\u00ednic\/IDIBAPS\/CIBERNED\/European Reference Network for Rare Neurological Diseases (ERN-RND)\/Institut de Neurocie\u0300ncies 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