{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:53:33Z","timestamp":1785405213894,"version":"3.56.0"},"reference-count":31,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"crossref","award":["DMR-111-104"],"award-info":[{"award-number":["DMR-111-104"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"crossref","award":["CMUHCH-CMU-115-005"],"award-info":[{"award-number":["CMUHCH-CMU-115-005"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"crossref"}]},{"award":["DMR-111-104"],"award-info":[{"award-number":["DMR-111-104"]}],"id":[{"id":"https:\/\/ror.org\/0368s4g32","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CMUHCH-CMU-115-005"],"award-info":[{"award-number":["CMUHCH-CMU-115-005"]}],"id":[{"id":"https:\/\/ror.org\/0368s4g32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) lacks effective therapeutic methods. Exosomes are specialized vesicles that feature a double-layered lipid structure and are rich in proteins, miRNA, mRNA, growth factors, and other biomolecules. Their diverse components enable tissue repair and cell activation, making exosomes a promising candidate for therapeutic applications, including for PD. Exosomes are widely studied in cancer treatment and regenerative medicine. Since these vesicles retain the characteristics of their source cells, selecting the appropriate cell type is crucial. In this study, we compared exosomes derived from induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and 293T cells in terms of particle production, protein content, cellular uptake efficiency, and therapeutic effects on PD. The results showed that exosomes derived from iPSCs outperformed those from the other two cell types in all evaluated aspects, followed by MSC-derived exosomes, while 293T-derived exosomes were the least effective. This study provides valuable comparative data to inform the selection of source cells for exosome-based therapies in regenerative medicine.<\/jats:p>","DOI":"10.3390\/ijms27104212","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Comparative Analysis of iPSC, MSC, and 293T-Derived Exosomes for Parkinson\u2019s Disease Therapy"],"prefix":"10.3390","volume":"27","author":[{"given":"Kuan-Fei","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Science, China Medical University, Taichung 411, Taiwan"},{"name":"Department of Neurology, China Medical University Hospital, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8517-754X","authenticated-orcid":false,"given":"Syuan-Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan-Hao","family":"Kuo","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woei-Cherng","family":"Shyu","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-Bin","family":"Jeng","sequence":"additional","affiliation":[{"name":"Cell Therapy Center, China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Organ Transplantation Center, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5803-4460","authenticated-orcid":false,"given":"Shih-Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Ph.D. Program for Aging, College of Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"Neuroscience and Brain Disease Center, College of Medicine, China Medical University, Taichung 411, Taiwan"},{"name":"Office of Research and Development, Asia University, Taichung 413, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/0022-510X(73)90175-5","article-title":"Brain dopamine and the syndromes of Parkinson and Huntington Clinical, morphological and neurochemical correlations","volume":"20","author":"Bernheimer","year":"1973","journal-title":"J. Neurol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/334345a0","article-title":"Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson\u2019s disease","volume":"334","author":"Hirsch","year":"1988","journal-title":"Nature"},{"key":"ref_3","first-page":"1192","article-title":"Survival and differentiation of transplanted neural stem cells in mice brain with MPTP-induced Parkinson disease","volume":"24","author":"Li","year":"2003","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3410\/B3-15","article-title":"Exosomes: Secreted vesicles and intercellular communications","volume":"3","author":"Thery","year":"2011","journal-title":"F1000 Biol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1172\/JCI81136","article-title":"Exosomes and tumor-mediated immune suppression","volume":"126","author":"Whiteside","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103133","DOI":"10.1016\/j.arr.2026.103133","article-title":"Mechanistic Research and Therapeutic Prospects of Alternative Splicing in Neurodegenerative Diseases","volume":"118","author":"Ran","year":"2026","journal-title":"Ageing Res. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"26913","DOI":"10.3402\/jev.v3.26913","article-title":"Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the International Society for Extracellular Vesicles","volume":"3","author":"Lotvall","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chen, H., Yao, H., Chi, J., Li, C., Liu, Y., Yang, J., Yu, J., Wang, J., Ruan, Y., and Pi, J. (2023). Engineered exosomes as drug and RNA co-delivery system: New hope for enhanced therapeutics? Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1254356"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ding, Y., Luo, Q., Que, H., Wang, N., Gong, P., and Gu, J. (2022). Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Agent for the Treatment of Liver Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810972"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1161\/CIRCRESAHA.117.312394","article-title":"Induced Pluripotent Stem Cells Derived Extracellular Vesicles: A Potential Therapy for Cardiac Repair","volume":"122","author":"Garikipati","year":"2018","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1021\/acschemneuro.8b00469","article-title":"Exosomes in Parkinson\u2019s Disease: Current Perspectives and Future Challenges","volume":"10","author":"Yuan","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00401-014-1314-y","article-title":"Plasma exosomal alpha-synuclein is likely CNS-derived and increased in Parkinson\u2019s disease","volume":"128","author":"Shi","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jconrel.2015.03.033","article-title":"Exosomes as drug delivery vehicles for Parkinson\u2019s disease therapy","volume":"207","author":"Haney","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1016\/j.scib.2024.10.027","article-title":"Targeting modulation of intestinal flora through oral route by an antimicrobial nucleic acid-loaded exosome-like nanovesicles to improve Parkinson\u2019s disease","volume":"69","author":"Cui","year":"2024","journal-title":"Sci. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1007\/s12035-014-9054-5","article-title":"Exosomes as a Nanodelivery System: A Key to the Future of Neuromedicine?","volume":"53","author":"Aryani","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1186\/s12951-024-02955-x","article-title":"Genetically modified E. Coli secreting melanin (E.melanin) activates the astrocytic PSAP-GPR37L1 pathway and mitigates the pathogenesis of Parkinson\u2019s disease","volume":"22","author":"Kong","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nprot.2006.342","article-title":"Protocol for the MPTP mouse model of Parkinson\u2019s disease","volume":"2","author":"Przedborski","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/aps.2017.49","article-title":"Reassessment of subacute MPTP-treated mice as animal model of Parkinson\u2019s disease","volume":"38","author":"Zhang","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1749-6632.2003.tb07471.x","article-title":"Apoptosis inducing factor and PARP-mediated injury in the MPTP mouse model of Parkinson\u2019s disease","volume":"991","author":"Wang","year":"2003","journal-title":"Ann. N. Y Acad. Sci."},{"key":"ref_23","first-page":"19","article-title":"MPTP mouse models of Parkinson\u2019s disease: An update","volume":"1","author":"Meredith","year":"2011","journal-title":"J. Park. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.bbr.2014.12.035","article-title":"Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson\u2019s disease","volume":"281","author":"Liu","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1186\/s12951-024-02697-w","article-title":"IPSC-NSCs-derived exosomal let-7b-5p improves motor function after spinal cord Injury by modulating microglial\/macrophage pyroptosis","volume":"22","author":"Liu","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev-pharmtox-061616-030146","article-title":"Stem Cell Extracellular Vesicles: Extended Messages of Regeneration","volume":"57","author":"Riazifar","year":"2017","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41419-020-2473-5","article-title":"Exosomes derived from mesenchymal stem cells repair a Parkinson\u2019s disease model by inducing autophagy","volume":"11","author":"Chen","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.stem.2020.09.014","article-title":"Pluripotent Stem Cell-Based Cell Therapy-Promise and Challenges","volume":"27","author":"Yamanaka","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1002\/mds.25978","article-title":"Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice","volume":"29","author":"Cooper","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101566","DOI":"10.1016\/j.dcn.2025.101566","article-title":"Neural, cognitive and psychopathological signatures of a prosocial or delinquent peer environment during early adolescence","volume":"73","author":"Liu","year":"2025","journal-title":"Dev. Cogn. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41420-024-02176-z","article-title":"Neural stem cells derived from alpha-synuclein-knockdown iPS cells alleviate Parkinson\u2019s disease","volume":"10","author":"Wang","year":"2024","journal-title":"Cell Death Discov."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4212\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:14:22Z","timestamp":1778645662000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,9]]},"references-count":31,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104212"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104212","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,9]]}}}