Intracerebroventricular delivery of hematopoietic progenitors results in rapid and robust engraftment of microglia-like cells.
Sci Adv
; 3(12): e1701211, 2017 12.
Article
in En
| MEDLINE
| ID: mdl-29226242
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cerebral Ventricles
/
Microglia
/
Hematopoietic Stem Cell Transplantation
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Sci Adv
Year:
2017
Document type:
Article
Affiliation country:
Italy