{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:20:57Z","timestamp":1792977657818,"version":"4.5.0"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"21","funder":[{"name":"NIH, Research to Prevent Blindness, The Center for Medical Genomics at IU School of Medicine","award":["NIH grants: EY0126001,EY007739,HL110170"],"award-info":[{"award-number":["NIH grants: EY0126001,EY007739,HL110170"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:p>\n                    Retinopathy of prematurity (ROP) is a disorder of the developing retina of preterm infants. ROP can lead to blindness because of abnormal angiogenesis that is the result of suspended vascular development and vaso-obliteration leading to severe retinal stress and hypoxia. We tested the hypothesis that the use of the human progenitor cell combination, bone marrow\u2013derived CD34\n                    <jats:sup>+<\/jats:sup>\n                    cells and vascular wall\u2013derived endothelial colony\u2013forming cells (ECFCs), would synergistically protect the developing retinal vasculature in a mouse model of ROP, called oxygen-induced retinopathy (OIR). CD34\n                    <jats:sup>+<\/jats:sup>\n                    cells alone, ECFCs alone, or the combination thereof were injected intravitreally at either P5 or P12 and pups were euthanized at P17. Retinas from OIR mice injected with ECFCs or the combined treatment revealed formation of the deep vascular plexus (DVP) while still in hyperoxia, with normal-appearing connections between the superficial vascular plexus (SVP) and the DVP. In addition, the combination of cells completely prevented aberrant retinal neovascularization and was more effective anatomically and functionally at rescuing the ischemia phenotype than either cell type alone. We show that the beneficial effects of the cell combination are the result of their ability to orchestrate an acceleration of vascular development and more rapid ensheathment of pericytes on the developing vessels. Lastly, our proteomic and transcriptomic data sets reveal pathways altered by the dual cell therapy, including many involved in neuroretinal maintenance, and principal component analysis (PCA) showed that cell therapy restored OIR retinas to a state that was closely associated with age-matched normal retinas. Together, these data herein support the use of dual cell therapy as a promising preventive treatment for the development of ROP in premature infants.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.129224","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T11:01:33Z","timestamp":1572519693000},"source":"Crossref","is-referenced-by-count":31,"title":["Progenitor cell combination normalizes retinal vascular development in the oxygen-induced retinopathy (OIR) model"],"prefix":"10.1172","volume":"4","author":[{"given":"Sergio","family":"Li Calzi","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn C.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1967-2408","authenticated-orcid":true,"given":"Leni","family":"Moldovan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Shelley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-124X","authenticated-orcid":true,"given":"Lyne","family":"Racette","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith L.","family":"Quigley","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth D.","family":"Fortmann","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0796-1766","authenticated-orcid":true,"given":"Michael E.","family":"Boulton","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervin C.","family":"Yoder","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria B.","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2019,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1095-1024"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208129"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60178-6"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.11.001"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.187"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2016.10.002"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1254"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1414"},{"issue":"1","key":"B9","first-page":"50","article-title":"The definition of EPCs and other bone marrow cells contributing to neoangiogenesis and tumor growth: is there common ground for understanding the roles of numerous marrow-derived cells in the neoangiogenic process?","volume":"1796","author":"Yoder","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-043471"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0340"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-04-1396"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2008.12.009"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.1186\/1755-8794-3-18","article-title":"Molecular analysis of endothelial progenitor cell (EPC) subtypes reveals two distinct cell populations with different identities","volume":"3","author":"Medina","year":"2010","journal-title":"BMC Med Genomics"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.503433"},{"issue":"3","key":"B16","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.90905","article-title":"Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown","volume":"2","author":"Ogura","year":"2017","journal-title":"JCI Insight"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21698"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2014.921312"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-1855"},{"issue":"1","key":"B20","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19010110","article-title":"The role of microglia in diabetic retinopathy: inflammation, microvasculature defects and neurodegeneration","volume":"19","author":"Altmann","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nature22078"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/80639"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00084-8"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-02-00455.1993"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0936-16.2016"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011046200"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0446"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(03)00002-2"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026674"},{"issue":"5","key":"B30","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1242\/dev.122.5.1427","article-title":"Effects of GGF\/neuregulins on neuronal survival and neurite outgrowth correlate with erbB2\/neu expression in developing rat retina","volume":"122","author":"Bermingham-McDonogh","year":"1996","journal-title":"Development"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25575"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004143107"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000137877.89448.78"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405388111"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00809-1"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5176"},{"issue":"2","key":"B37","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.89906","article-title":"CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect","volume":"2","author":"Sakimoto","year":"2017","journal-title":"JCI Insight"},{"issue":"1","key":"B38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1179\/135100007X162167","article-title":"Modulation of antioxidant gene expression by 4-hydroxynonenal: atheroprotective role of the Nrf2\/ARE transcription pathway","volume":"12","author":"Siow","year":"2007","journal-title":"Redox Rep"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2007.04.002"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1307574110"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2015.0168"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/129224\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:22:51Z","timestamp":1779193371000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/129224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,1]]},"references-count":41,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2019,11,1]]},"published-print":{"date-parts":[[2019,11,1]]}},"alternative-id":["10.1172\/jci.insight.129224"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.129224","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,1]]},"article-number":"e129224"}}