{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:57:05Z","timestamp":1780984625244,"version":"3.54.1"},"reference-count":123,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01AG071228-02"],"award-info":[{"award-number":["R01AG071228-02"]}]},{"name":"NIH","award":["1R01AG081356-01A1"],"award-info":[{"award-number":["1R01AG081356-01A1"]}]},{"name":"NIH","award":["1U24AG092191-01"],"award-info":[{"award-number":["1U24AG092191-01"]}]},{"name":"Lejeune Foundation","award":["GRT-2023b\/2277"],"award-info":[{"award-number":["GRT-2023b\/2277"]}]},{"name":"JSPS Grant-in-Aid for Exploratory Research","award":["24K22090"],"award-info":[{"award-number":["24K22090"]}]},{"name":"JSPS Grant-in-Aid for Scientific Research","award":["24K03259"],"award-info":[{"award-number":["24K03259"]}]},{"name":"The Mark Heider Foundation"},{"name":"Movement Disorder Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Cell replacement therapy is a promising investigational approach for Parkinson\u2019s disease (PD), a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra. Although current PD therapies provide symptomatic relief, none halt or reverse disease progression. Early transplantation studies using fetal dopaminergic neurons provided proof of concept for PD cell replacement, with recent efforts focusing on pluripotent stem cell-derived dopaminergic progenitors that are now entering clinical testing. These strategies face challenges, however, including immune compatibility, tumorigenic risk, and the need for controlled differentiation and functional integration. Multi-lineage differentiating stress-enduring (Muse) cells are endogenous, non-tumorigenic pluripotent-like stem cells that home to sites of tissue injury and differentiate in response to the host microenvironment. A targeted literature search of PubMed and Scopus, however, did not identify prior reviews specifically addressing Muse cells in the context of PD, highlighting a gap in the literature. Here, we examine current limitations of established cell-replacement approaches and consider whether Muse cells may represent a mechanistically distinct cell source. Early clinical studies of Muse cell therapy in stroke and amyotrophic lateral sclerosis suggest an encouraging safety profile and preliminary signals of potential therapeutic benefit, although these findings are based on small, early-stage trials and require confirmation. The evidence supporting Muse cell therapy in PD is currently limited to a single preclinical animal study, supported by mechanistic in vitro findings and indirect evidence from other neurologic disease models; therefore, its relevance to PD remains to be established, and current evidence is insufficient to support conclusions regarding clinical efficacy. Together, these observations provide a rationale for further targeted preclinical investigation and support the systematic evaluation of Muse cells as a mechanistically distinct candidate for regenerative therapy in PD.<\/jats:p>","DOI":"10.3390\/jcm15114370","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:43:04Z","timestamp":1780648984000},"page":"4370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stem Cell Therapy for Parkinson\u2019s Disease: A Mechanistically Distinct Role for Muse Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4182-7413","authenticated-orcid":false,"given":"Michael H.","family":"Mesches","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-7599","authenticated-orcid":false,"given":"Ann-Charlotte","family":"Granholm","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9635-8001","authenticated-orcid":false,"given":"Daniel","family":"Paredes","sequence":"additional","affiliation":[{"name":"Knoebel Institute for Healthy Aging, University of Denver, Denver, CO 80208, USA"},{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Mesches","sequence":"additional","affiliation":[{"name":"SciTechEdit International LLC, Highlands Ranch, CO 80130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yo","family":"Oguma","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Dezawa","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.neurol.2015.09.012","article-title":"Epidemiology of Parkinson\u2019s disease","volume":"172","author":"Elbaz","year":"2016","journal-title":"Rev. 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