FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2988758321> ?p ?o ?g. }

• W2988758321 endingPage "5599" @default.
• W2988758321 startingPage "5599" @default.
• W2988758321 abstract "Background: Insufficient thymic function of allogeneic hematopoietic stem cell transplantation (allo-HSCT) receptors results in continuous production of alloreactive T cells, which leads to the development of graft-versus-host disease (GVHD), especially chronic GVHD (cGVHD). We have previously found that patients with acute GVHD (aGVHD) treated with mesenchymal stem cells (MSCs) have increased thymic output and decreased incidence of cGVHD, thus hypothesized that MSCs may reduce the incidence of cGVHD by remodeling the thymus. Chemokine receptor 9 (CCR9), the receptor that specifically guides migration of T-lineage precursors into thymus, is also expressed on MSCs, and thus may be a key factor mediating MSCs homing to the thymus. This in turn allows MSCs to reduce GVHD by repairing thymus tissue structure and saving thymus function. Methods: We carried out studies in a murine GVHD model of fully MHC-mismatched myeloablative bone marrow transplantation (C57BL/6 to BALB/c), a model that can observe the prolongation of aGVHD to cGVHD. We randomly divided GVHD mice into four groups, including three MSCs treated groups and one untreated group. CCR9 over-expressed (MSC/CCR9+), knocked-down (MSC/CCR9-) and empty-load MSCs (MSC/Control) were generated and administrated intravenously at dose of 5 × 105 cells/infusion at 7th and 21th day post HCT to the treated groups respectively to compare their thymic homing ability, and therapeutic effects of GVHD with the untreated group. Clinical scores were recorded once every five days to evaluate GVHD symptoms. Mice of MSCs treated groups and the untreated group were sacrificed at 30d, 45d and 60d after HCT. Thymuses of each group were collected and assessed for size and weight before being manufactured into frozen sections or thymic single-cell suspension. We then analyzed the number and distribution of MSCs in the thymus of the treated groups to assess the role of CCR9 in thymic homing, and analyzed the expression of thymic T cells subsets (CD4+CD8-, CD4-CD8+, CD4+CD8+ T, CD4+CD25+Foxp3+Tregs), thymic epithelial cells (TECs) substes (CD45-CD326+Ly51+ cortical TECs and CD45-CD326+UEA-1+ medullary TECs) and the level of T cell receptor rearrangement excision circles (TRECs) in thymus among the four groups to evaluate the repair effect of MSCs for thymus. Radiation-pretreated murine TECs were cultured alone or co-cultured with murine MSCs in vitro to assess the effect of MSCs on damaged TECs. Results: The infusion of MSC/CCR9+ potently alleviated the clinical signs of GVHD and prolonged the survival of GVHD mice (P<0.05 versus MSC/CCR9- and untreated group). Significant increases in thymus size and weight were observed in the MSC/CCR9+ group, as well as the number of total thymocytes and the more organized cortical medullary structure compared to the other groups. MSCs enter the thymus from the microvascular region at the cortex-medium junction. MSC/CCR9+ were found to appear in the cortex-medium junction of thymus in a greater amount 24 hours after the first infusion, then distribute throughout the whole thymus and relocate in proximity with TECs 48 hours thereafter. MSC/Control could be observed in the cortical and cortex-medium junction, whereas MSC/CCR9- was observed only in the cortex-medium junction with a small amount of distribution. Immunofluorescence of thymus frozen sections showed that, compared with other groups, TECs had decreased apoptosis and significantly increased proliferation and maturation levels in MSC/CCR9+ group, indicating MSCs potently repaired injured TECs and promoted their proliferation and maturation. The number of TECs and its proportion of thymus stroma were significantly improved, including cortical TEC and medullary TECs. As for thymocyte, MSC/CCR9+ infusion significantly increased the number and proportion of CD4+CD8+T cells and Tregs, which were reported deficiency in GVHD thymus. Furthermore, MSC/CCR9+ administration resulted in a remarkable increase in the levels of TRECs in the thymocyte at 45d and 60d after HCT (P<0.05 versus MSC/CCR9- and untreated group). In vitro study showed co-cultured TECs had a decreased apoptosis and increased proliferation compared to TECs cultured alone. Conclusion: This study demonstrates that CCR9 plays an important role in guiding migration of MSCs to thymus and thus highly intensify their issue repair and immunomodulatory effect to rescue thymus function in GVHD model. Disclosures No relevant conflicts of interest to declare." @default.
• W2988758321 created "2019-11-22" @default.
• W2988758321 creator A5006651636 @default.
• W2988758321 creator A5032457247 @default.
• W2988758321 creator A5041130348 @default.
• W2988758321 creator A5065034568 @default.
• W2988758321 creator A5073479438 @default.
• W2988758321 date "2019-11-13" @default.
• W2988758321 modified "2023-09-27" @default.
• W2988758321 title "Mesenchymal Stem Cells Improve the Structure and Function of the Graft-Versus-Host Disease Receptor Thymus: CCR9 Plays an Important Role in Its Homing Thymus" @default.
• W2988758321 doi "https://doi.org/10.1182/blood-2019-125307" @default.
• W2988758321 hasPublicationYear "2019" @default.
• W2988758321 type Work @default.
• W2988758321 sameAs 2988758321 @default.
• W2988758321 citedByCount "1" @default.
• W2988758321 countsByYear W29887583212021 @default.
• W2988758321 crossrefType "journal-article" @default.
• W2988758321 hasAuthorship W2988758321A5006651636 @default.
• W2988758321 hasAuthorship W2988758321A5032457247 @default.
• W2988758321 hasAuthorship W2988758321A5041130348 @default.
• W2988758321 hasAuthorship W2988758321A5065034568 @default.
• W2988758321 hasAuthorship W2988758321A5073479438 @default.
• W2988758321 hasBestOaLocation W29887583211 @default.
• W2988758321 hasConcept C109159458 @default.
• W2988758321 hasConcept C126322002 @default.
• W2988758321 hasConcept C12823836 @default.
• W2988758321 hasConcept C129470790 @default.
• W2988758321 hasConcept C13373296 @default.
• W2988758321 hasConcept C142724271 @default.
• W2988758321 hasConcept C151872237 @default.
• W2988758321 hasConcept C18903297 @default.
• W2988758321 hasConcept C198826908 @default.
• W2988758321 hasConcept C203014093 @default.
• W2988758321 hasConcept C2777408962 @default.
• W2988758321 hasConcept C2779972918 @default.
• W2988758321 hasConcept C2780007613 @default.
• W2988758321 hasConcept C28328180 @default.
• W2988758321 hasConcept C2911091166 @default.
• W2988758321 hasConcept C54355233 @default.
• W2988758321 hasConcept C71924100 @default.
• W2988758321 hasConcept C86803240 @default.
• W2988758321 hasConcept C8891405 @default.
• W2988758321 hasConceptScore W2988758321C109159458 @default.
• W2988758321 hasConceptScore W2988758321C126322002 @default.
• W2988758321 hasConceptScore W2988758321C12823836 @default.
• W2988758321 hasConceptScore W2988758321C129470790 @default.
• W2988758321 hasConceptScore W2988758321C13373296 @default.
• W2988758321 hasConceptScore W2988758321C142724271 @default.
• W2988758321 hasConceptScore W2988758321C151872237 @default.
• W2988758321 hasConceptScore W2988758321C18903297 @default.
• W2988758321 hasConceptScore W2988758321C198826908 @default.
• W2988758321 hasConceptScore W2988758321C203014093 @default.
• W2988758321 hasConceptScore W2988758321C2777408962 @default.
• W2988758321 hasConceptScore W2988758321C2779972918 @default.
• W2988758321 hasConceptScore W2988758321C2780007613 @default.
• W2988758321 hasConceptScore W2988758321C28328180 @default.
• W2988758321 hasConceptScore W2988758321C2911091166 @default.
• W2988758321 hasConceptScore W2988758321C54355233 @default.
• W2988758321 hasConceptScore W2988758321C71924100 @default.
• W2988758321 hasConceptScore W2988758321C86803240 @default.
• W2988758321 hasConceptScore W2988758321C8891405 @default.
• W2988758321 hasIssue "Supplement_1" @default.
• W2988758321 hasLocation W29887583211 @default.
• W2988758321 hasOpenAccess W2988758321 @default.
• W2988758321 hasPrimaryLocation W29887583211 @default.
• W2988758321 hasRelatedWork W198187582 @default.
• W2988758321 hasRelatedWork W2031513730 @default.
• W2988758321 hasRelatedWork W2253826012 @default.
• W2988758321 hasRelatedWork W2379234955 @default.
• W2988758321 hasRelatedWork W2390445321 @default.
• W2988758321 hasRelatedWork W2910362092 @default.
• W2988758321 hasRelatedWork W3010500197 @default.
• W2988758321 hasRelatedWork W4214770150 @default.
• W2988758321 hasRelatedWork W4310851686 @default.
• W2988758321 hasRelatedWork W1121952681 @default.
• W2988758321 hasVolume "134" @default.
• W2988758321 isParatext "false" @default.
• W2988758321 isRetracted "false" @default.
• W2988758321 magId "2988758321" @default.
• W2988758321 workType "article" @default.