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The dysfunction or loss of oligodendrocytes leads to demyelinating diseases such as multiple sclerosis (MS). To treat demyelinating diseases, the development of a therapy that promotes remyelination is required. In the present study, we established an in vitro method to convert human fibroblasts into induced oligodendrocyte-like cells (iOLCs) in 3 days. The induced cells displayed morphologies and molecular signatures similar to oligodendrocytes after treatment with valproic acid and exposure to the small molecules Y27632, SU9516, and forskolin (FSK). To pursue the development of a cell-free remyelination therapy in vivo, we used a cuprizone-induced demyelinated mouse model. The small molecules (Y27632, SU9516, and FSK) were directly injected into the demyelinated corpus callosum of the mouse brain. This combination of small molecules rescued the demyelination phenotype within two weeks as observed by light and electron microscopy. These results provide a foundation for exploring the development of a treatment for demyelinating diseases via regenerative medicine.<\/jats:p>","DOI":"10.3390\/cells11071091","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:05:18Z","timestamp":1648166718000},"page":"1091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model"],"prefix":"10.3390","volume":"11","author":[{"given":"Pei-Lun","family":"Lai","sequence":"first","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2176-8655","authenticated-orcid":false,"given":"Chi-Hou","family":"Ng","sequence":"additional","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan"},{"name":"Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei 10617, Taiwan"},{"name":"Department of Life Science, Institute of Molecular and Cellular Biology, College of Life Science, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8389-6599","authenticated-orcid":false,"given":"Chia-Hsin","family":"Wu","sequence":"additional","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan"},{"name":"Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Ying","family":"Lai","sequence":"additional","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott C.","family":"Schuyler","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Division of Head and Neck Surgery, Department of Otolaryngology, Chang Gung Memorial Hospital, Taoyuan 33302, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicki","family":"Wang","sequence":"additional","affiliation":[{"name":"Translational Medicine, National Defense Medical Center, Academia Sinica, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-8040","authenticated-orcid":false,"given":"Hsuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University, Academia Sinica, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueh-Chang","family":"Lee","sequence":"additional","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan"},{"name":"Department of Ophthalmology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Hsi","family":"Chuang","sequence":"additional","affiliation":[{"name":"College of Management, Chung Hua University, Hsinchu 30012, Taiwan"},{"name":"Gwo Xi Stem Cell Applied Technology Co., Ltd., Hsinchu 30261, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Huan","family":"Yang","sequence":"additional","affiliation":[{"name":"Gwo Xi Stem Cell Applied Technology Co., Ltd., Hsinchu 30261, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-3440","authenticated-orcid":false,"given":"Hsiao-Chun","family":"Huang","sequence":"additional","affiliation":[{"name":"Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei 10617, Taiwan"},{"name":"Department of Life Science, Institute of Molecular and Cellular Biology, College of Life Science, National Taiwan University, Taipei 10617, Taiwan"},{"name":"Graduate Institute of Electronics Engineering, College of Electrical Engineering and Computer Science, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Lu","sequence":"additional","affiliation":[{"name":"Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan"},{"name":"Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, 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