{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:13:57Z","timestamp":1790151237535,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008358","name":"Hersenstichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008358","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>In metachromatic leukodystrophy, a lysosomal storage disorder due to decreased arylsulfatase A activity, hematopoietic stem cell transplantation may stop brain demyelination and allow remyelination, thereby halting white matter degeneration. This is the first study to define the effects and therapeutic mechanisms of hematopoietic stem cell transplantation on brain tissue of transplanted metachromatic leukodystrophy patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Autopsy brain tissue was obtained from eight (two transplanted and six nontransplanted) metachromatic leukodystrophy patients, and two age\u2010matched controls. We examined the presence of donor cells by immunohistochemistry and microscopy. In addition, we assessed myelin content, oligodendrocyte numbers, and macrophage phenotypes. An unpaired\n                      <jats:italic>t<\/jats:italic>\n                      \u2010test, linear regression or the nonparametric Mann\u2013Whitney\n                      <jats:italic>U<\/jats:italic>\n                      \u2010test was performed to evaluate differences between the transplanted, nontransplanted, and control group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In brain tissue of transplanted patients, we found metabolically competent donor macrophages expressing arylsulfatase A distributed throughout the entire white matter. Compared to nontransplanted patients, these macrophages preferentially expressed markers of alternatively activated, anti\u2010inflammatory cells that may support oligodendrocyte survival and differentiation. Additionally, transplanted patients showed higher numbers of oligodendrocytes and evidence for remyelination. Contrary to the current hypothesis on therapeutic mechanism of hematopoietic cell transplantation in metachromatic leukodystrophy, we detected no enzymatic cross\u2010correction to resident astrocytes and oligodendrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>In conclusion, donor macrophages are able to digest accumulated sulfatides and may play a neuroprotective role for resident oligodendrocytes, thereby enabling remyelination, albeit without evidence of cross\u2010correction of oligo\u2010 and astroglia. These results emphasize the importance of immunomodulation in addition to the metabolic correction, which might be exploited for improved outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.50975","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T11:25:54Z","timestamp":1579692354000},"page":"169-180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Metachromatic leukodystrophy and transplantation: remyelination, no cross\u2010correction"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-0728","authenticated-orcid":false,"given":"Nicole I.","family":"Wolf","sequence":"first","affiliation":[{"name":"Department of Child Neurology Center for Childhood White Matter Diseases Emma Children\u2019s Hospital Amsterdam University Medical Centers Vrije Universiteit Amsterdam, and Amsterdam Neuroscience Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein","family":"Breur","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Center for Childhood White Matter Diseases Emma Children\u2019s Hospital Amsterdam University Medical Centers Vrije Universiteit Amsterdam, and Amsterdam Neuroscience Amsterdam The Netherlands"},{"name":"Department of Pathology Amsterdam Neuroscience Amsterdam University Medical Centers Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Plug","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Center for Childhood White Matter Diseases Emma Children\u2019s Hospital Amsterdam University Medical Centers Vrije Universiteit Amsterdam, and Amsterdam Neuroscience Amsterdam The Netherlands"},{"name":"Department of Pathology Amsterdam Neuroscience Amsterdam University Medical Centers Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-6784","authenticated-orcid":false,"given":"Shanice","family":"Beerepoot","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Center for Childhood White Matter Diseases Emma Children\u2019s Hospital Amsterdam University Medical Centers Vrije Universiteit Amsterdam, and Amsterdam Neuroscience Amsterdam The Netherlands"},{"name":"Center for Translational Immunology University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee S. R.","family":"Westerveld","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Center for Childhood White Matter Diseases Emma Children\u2019s Hospital Amsterdam University Medical Centers Vrije Universiteit Amsterdam, and Amsterdam Neuroscience Amsterdam The Netherlands"},{"name":"Department of Pathology Amsterdam Neuroscience Amsterdam University Medical Centers Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane F.","family":"van Rappard","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Center for Childhood White Matter Diseases Emma Children\u2019s Hospital Amsterdam University Medical Centers Vrije Universiteit Amsterdam, and Amsterdam Neuroscience Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon I.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Axonal Signaling Netherlands Institute for Neuroscience Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten H. P.","family":"Kole","sequence":"additional","affiliation":[{"name":"Department of Axonal Signaling Netherlands Institute for Neuroscience Amsterdam The Netherlands"},{"name":"Cell Biology Faculty of Science Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Vanderver","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Pediatrics Children\u2019s Hospital of Philadelphia University of Pennsylvania Philadelphia Pennsylvania"},{"name":"Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo S.","family":"van der Knaap","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Center for Childhood White Matter Diseases Emma Children\u2019s Hospital Amsterdam University Medical Centers Vrije Universiteit Amsterdam, and Amsterdam Neuroscience 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