Matches in SemOpenAlex for { <https://semopenalex.org/work/W2563765725> ?p ?o ?g. }
Showing items 1 to 75 of
75
with 100 items per page.
- W2563765725 abstract "Cystinosis is a lysosomal storage disorder resulting from genetic mutations in the ubiquitously expressed CTNS gene, which encodes the lysosomal transmembrane transporter called cystinosin. In the absence of functional cystinosin, cystine accumulates in all tissues of the body, eventually depositing as crystals. Thus, cystinosis is a multisystemic degenerative disorder, with end-stage kidney failure as the cardinal manifestation.Our previous work has shown that transplantation of syngeneic wild-type hematopoietic stem cells (HSCs) in the mouse model of cystinosis, Ctns-/- mice, was effective in treating cystinosis and led to long-term tissue preservation. Our study clearly established that transplanted HSCs integrated abundantly into all tissues and differentiated into tissue-resident macrophages, such as Kupffer cells in the liver, microglia in the brain, and dendritic cells in the kidney. Addressing the cellular mechanism, we showed that HSC-derived macrophages corrected the genetic defect by delivering functional cystinosin to adjacent host Ctns-/- cells via long intercellular bridges called tunneling nanotubes (TNTs). In the kidney, TNTs were shown to transfer cystinosin-containing lysosomes from transplanted interstitial macrophages into diseased proximal tubular cells directly across the dense, continuous, and formidable barrier of the tubular basement membrane. This is the first demonstration of correction of a genetic lysosomal defect by vesicular exchange via TNTs and suggests broader potential for HSC transplantation for other disorders due to defective vesicular proteins.Overall, correlation between differentiation of HSCs into macrophages and improved biochemical, functional, and anatomical outcomes post-transplantation suggest that macrophages are key mediators of tissue repair. To test this hypothesis and to characterize the molecular protagonists involved, Ctns-/- mice have been transplanted with HSCs isolated from mouse strains that are deficient in macrophage differentiation. This work will open new perspectives in regenerative medicine that could spur the development of novel stem cell-based therapy." @default.
- W2563765725 created "2017-01-06" @default.
- W2563765725 creator A5025976004 @default.
- W2563765725 creator A5040682034 @default.
- W2563765725 creator A5053979076 @default.
- W2563765725 creator A5062133346 @default.
- W2563765725 date "2015-05-01" @default.
- W2563765725 modified "2023-09-25" @default.
- W2563765725 title "277. Characterization of the Macrophage Response in Hematopoietic Stem Cell-Mediated Tissue Repair in Cystinosis" @default.
- W2563765725 doi "https://doi.org/10.1016/s1525-0016(16)33886-2" @default.
- W2563765725 hasPublicationYear "2015" @default.
- W2563765725 type Work @default.
- W2563765725 sameAs 2563765725 @default.
- W2563765725 citedByCount "0" @default.
- W2563765725 crossrefType "journal-article" @default.
- W2563765725 hasAuthorship W2563765725A5025976004 @default.
- W2563765725 hasAuthorship W2563765725A5040682034 @default.
- W2563765725 hasAuthorship W2563765725A5053979076 @default.
- W2563765725 hasAuthorship W2563765725A5062133346 @default.
- W2563765725 hasBestOaLocation W25637657251 @default.
- W2563765725 hasConcept C109159458 @default.
- W2563765725 hasConcept C126322002 @default.
- W2563765725 hasConcept C142724271 @default.
- W2563765725 hasConcept C181199279 @default.
- W2563765725 hasConcept C2777608289 @default.
- W2563765725 hasConcept C2778518273 @default.
- W2563765725 hasConcept C2779201268 @default.
- W2563765725 hasConcept C28328180 @default.
- W2563765725 hasConcept C2911091166 @default.
- W2563765725 hasConcept C502942594 @default.
- W2563765725 hasConcept C55493867 @default.
- W2563765725 hasConcept C71924100 @default.
- W2563765725 hasConcept C86803240 @default.
- W2563765725 hasConcept C95444343 @default.
- W2563765725 hasConceptScore W2563765725C109159458 @default.
- W2563765725 hasConceptScore W2563765725C126322002 @default.
- W2563765725 hasConceptScore W2563765725C142724271 @default.
- W2563765725 hasConceptScore W2563765725C181199279 @default.
- W2563765725 hasConceptScore W2563765725C2777608289 @default.
- W2563765725 hasConceptScore W2563765725C2778518273 @default.
- W2563765725 hasConceptScore W2563765725C2779201268 @default.
- W2563765725 hasConceptScore W2563765725C28328180 @default.
- W2563765725 hasConceptScore W2563765725C2911091166 @default.
- W2563765725 hasConceptScore W2563765725C502942594 @default.
- W2563765725 hasConceptScore W2563765725C55493867 @default.
- W2563765725 hasConceptScore W2563765725C71924100 @default.
- W2563765725 hasConceptScore W2563765725C86803240 @default.
- W2563765725 hasConceptScore W2563765725C95444343 @default.
- W2563765725 hasLocation W25637657251 @default.
- W2563765725 hasOpenAccess W2563765725 @default.
- W2563765725 hasPrimaryLocation W25637657251 @default.
- W2563765725 hasRelatedWork W1973637452 @default.
- W2563765725 hasRelatedWork W1975071693 @default.
- W2563765725 hasRelatedWork W1979478822 @default.
- W2563765725 hasRelatedWork W1986437360 @default.
- W2563765725 hasRelatedWork W2007165528 @default.
- W2563765725 hasRelatedWork W2007459839 @default.
- W2563765725 hasRelatedWork W2021955237 @default.
- W2563765725 hasRelatedWork W2028664960 @default.
- W2563765725 hasRelatedWork W2048338507 @default.
- W2563765725 hasRelatedWork W2070777203 @default.
- W2563765725 hasRelatedWork W2122046893 @default.
- W2563765725 hasRelatedWork W2143095584 @default.
- W2563765725 hasRelatedWork W2150393481 @default.
- W2563765725 hasRelatedWork W2379022746 @default.
- W2563765725 hasRelatedWork W2404677669 @default.
- W2563765725 hasRelatedWork W2750484901 @default.
- W2563765725 hasRelatedWork W2790731412 @default.
- W2563765725 hasRelatedWork W2900561906 @default.
- W2563765725 hasRelatedWork W2918580568 @default.
- W2563765725 hasRelatedWork W2918926249 @default.
- W2563765725 isParatext "false" @default.
- W2563765725 isRetracted "false" @default.
- W2563765725 magId "2563765725" @default.
- W2563765725 workType "article" @default.