{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bhatwadekar AD"],"funding":["NEI NIH HHS","NIDDK NIH HHS","NHLBI NIH HHS"],"pagination":["2010-9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2911069"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["59(8)"],"pubmed_abstract":["<h4>Objective</h4>Peripheral blood CD34(+) cells from diabetic patients demonstrate reduced vascular reparative function due to decreased proliferation and diminished migratory prowess, largely resulting from decreased nitric oxide (NO) bioavailability. The level of TGF-beta, a key factor that modulates stem cell quiescence, is increased in the serum of type 2 diabetic patients. We asked whether transient TGF-beta1 inhibition in CD34(+) cells would improve their reparative ability.<h4>Research design and methods</h4>To inhibit TGF-beta1 protein expression, CD34(+) cells were treated ex vivo with antisense phosphorodiamidate morpholino oligomers (TGF-beta1-PMOs) and analyzed for cell surface CXCR4 expression, cell survival in the absence of added growth factors, SDF-1-induced migration, NO release, and in vivo retinal vascular reparative ability.<h4>Results</h4>TGF-beta1-PMO treatment of diabetic CD34(+) cells resulted in increased expression of CXCR4, enhanced survival in the absence of growth factors, and increased migration and NO release as compared with cells treated with control PMO. Using a retinal ischemia reperfusion injury model in mice, we observed that recruitment of diabetic CD34(+) cells to injured acellular retinal capillaries was greater after TGF-beta1-PMO treatment compared with control PMO-treated cells.<h4>Conclusions</h4>Transient inhibition of TGF-beta1 may represent a promising therapeutic strategy for restoring the reparative capacity of dysfunctional diabetic CD34(+) cells."],"journal":["Diabetes"],"pubmed_title":["Transient inhibition of transforming growth factor-beta1 in human diabetic CD34+ cells enhances vascular reparative functions."],"pmcid":["PMC2911069"],"funding_grant_id":["R01 EY007739","U01-HL-087366","R21 EY014818","R01 EY012601","EY-007739","R44 EY028070","EY-012601","R01 DK090730","U01 HL087366","RC1 EY020341"],"pubmed_authors":["Jarajapu YP","Ruscetti FW","Kennedy L","Higgins PJ","Bartelmez SH","Guerin EP","Sheridan C","Kent D","Grant MB","Lansang MC","Bhatwadekar AD","Caballero S","Pepine CJ"],"additional_accession":[]},"is_claimable":false,"name":"Transient inhibition of transforming growth factor-beta1 in human diabetic CD34+ cells enhances vascular reparative functions.","description":"<h4>Objective</h4>Peripheral blood CD34(+) cells from diabetic patients demonstrate reduced vascular reparative function due to decreased proliferation and diminished migratory prowess, largely resulting from decreased nitric oxide (NO) bioavailability. The level of TGF-beta, a key factor that modulates stem cell quiescence, is increased in the serum of type 2 diabetic patients. We asked whether transient TGF-beta1 inhibition in CD34(+) cells would improve their reparative ability.<h4>Research design and methods</h4>To inhibit TGF-beta1 protein expression, CD34(+) cells were treated ex vivo with antisense phosphorodiamidate morpholino oligomers (TGF-beta1-PMOs) and analyzed for cell surface CXCR4 expression, cell survival in the absence of added growth factors, SDF-1-induced migration, NO release, and in vivo retinal vascular reparative ability.<h4>Results</h4>TGF-beta1-PMO treatment of diabetic CD34(+) cells resulted in increased expression of CXCR4, enhanced survival in the absence of growth factors, and increased migration and NO release as compared with cells treated with control PMO. Using a retinal ischemia reperfusion injury model in mice, we observed that recruitment of diabetic CD34(+) cells to injured acellular retinal capillaries was greater after TGF-beta1-PMO treatment compared with control PMO-treated cells.<h4>Conclusions</h4>Transient inhibition of TGF-beta1 may represent a promising therapeutic strategy for restoring the reparative capacity of dysfunctional diabetic CD34(+) cells.","dates":{"release":"2010-01-01T00:00:00Z","publication":"2010 Aug","modification":"2021-03-07T08:35:55Z","creation":"2019-03-27T00:32:45Z"},"accession":"S-EPMC2911069","cross_references":{"pubmed":["20460428"],"doi":["10.2337/db10-0287"]}}