Intracerebroventricular delivery of hematopoietic progenitors results in rapid and robust engraftment of microglia-like cells

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Intracerebroventricular delivery of hematopoietic progenitors results in rapid and robust engraftment of microglia-like cells

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Title: Intracerebroventricular delivery of hematopoietic progenitors results in rapid and robust engraftment of microglia-like cells
Author: Capotondo, Alessia; Milazzo, Rita; Garcia-Manteiga, Jose M.; Cavalca, Eleonora; Montepeloso, Annita; Garrison, Brian S.; Peviani, Marco; Rossi, Derrick J.; Biffi, Alessandra

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Citation: Capotondo, Alessia, Rita Milazzo, Jose M. Garcia-Manteiga, Eleonora Cavalca, Annita Montepeloso, Brian S. Garrison, Marco Peviani, Derrick J. Rossi, and Alessandra Biffi. 2017. “Intracerebroventricular delivery of hematopoietic progenitors results in rapid and robust engraftment of microglia-like cells.” Science Advances 3 (12): e1701211. doi:10.1126/sciadv.1701211. http://dx.doi.org/10.1126/sciadv.1701211.
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Abstract: Recent evidence indicates that hematopoietic stem and progenitor cells (HSPCs) can serve as vehicles for therapeutic molecular delivery to the brain by contributing to the turnover of resident myeloid cell populations. However, such engraftment needs to be fast and efficient to exert its therapeutic potential for diseases affecting the central nervous system. Moreover, the nature of the cells reconstituted after transplantation and whether they could comprise bona fide microglia remain to be assessed. We demonstrate that transplantation of HSPCs in the cerebral lateral ventricles provides rapid engraftment of morphologically, antigenically, and transcriptionally dependable microglia-like cells. We show that the cells comprised within the hematopoietic stem cell compartment and enriched early progenitor fractions generate this microglia-like population when injected in the brain ventricles in the absence of engraftment in the bone marrow. This delivery route has therapeutic relevance because it increases the delivery of therapeutic molecules to the brain, as shown in a humanized animal model of a prototypical lysosomal storage disease affecting the central nervous system.
Published Version: doi:10.1126/sciadv.1701211
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721728/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34652006
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