{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:21:07Z","timestamp":1792128067863,"version":"4.4.0"},"reference-count":70,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T00:00:00Z","timestamp":1685836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"publisher","award":["TRAN1\u201008525"],"award-info":[{"award-number":["TRAN1\u201008525"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Demyelinating disorders are among the most common and debilitating diseases in neurology. Canavan disease (CD) is a lethal demyelinating disease caused by mutation of the aspartoacylase (\n                    <jats:italic>ASPA<\/jats:italic>\n                    ) gene, which leads to the accumulation of its substrate\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyl\u2010\n                    <jats:sc>l<\/jats:sc>\n                    \u2010aspartate (NAA), and consequently demyelination and vacuolation in the brain. In this study, hypoimmunogenic human induced pluripotent stem cell (iPSC)\u2010derived oligodendrocyte progenitor cells (OPC) are developed from a healthy donor as an \u201coff\u2010the\u2010shelf\u201d cell therapy. Hypoimmunogenic iPSCs are generated through CRISPR\/Cas9 editing of the human leukocyte antigen (HLA) molecules in healthy donor\u2010derived iPSCs and differentiated into OPCs. The OPCs are engrafted into the brains of CD (nur7) mice and exhibit widespread distribution in the brain. The engrafted OPCs mature into oligodendrocytes that express the endogenous wildtype\n                    <jats:italic>ASPA<\/jats:italic>\n                    gene. Consequently, the transplanted mice exhibit elevated human ASPA expression and enzymatic activity and reduced NAA level in the brain. The transplanted OPCs are able to rescue major pathological features of CD, including defective myelination, extensive vacuolation, and motor function deficits. Moreover, the hypoimmunogenic OPCs exhibit low immunogenicity both in vitro and in vivo. The hypoimmunogenic OPCs can be used as \u201coff\u2010the\u2010shelf\u201d universal donor cells to treat various CD patients and many other demyelinating disorders, especially autoimmune demyelinating diseases, such as multiple sclerosis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202206910","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T14:39:07Z","timestamp":1686148747000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Developing Hypoimmunogenic Human iPSC\u2010Derived Oligodendrocyte Progenitor Cells as an Off\u2010The\u2010Shelf Cell Therapy for Myelin Disorders"],"prefix":"10.1002","volume":"10","author":[{"given":"Lizhao","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Diseases Beckman Research Institute of City of Hope  1500 E. Duarte Rd. Duarte CA 91010 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfei","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases Beckman Research Institute of City of Hope  1500 E. Duarte Rd. Duarte CA 91010 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases Beckman Research Institute of City of Hope  1500 E. Duarte Rd. Duarte CA 91010 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qui","family":"Luong","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases Beckman Research Institute of City of Hope  1500 E. Duarte Rd. Duarte CA 91010 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases Beckman Research Institute of City of Hope  1500 E. Duarte Rd. Duarte CA 91010 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases Beckman Research Institute of City of Hope  1500 E. Duarte Rd. Duarte CA 91010 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases Beckman Research Institute of City of Hope  1500 E. Duarte Rd. 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