{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:53:24Z","timestamp":1786978404022,"version":"build-2736575974"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":523,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100002020","name":"Children's Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002020","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Faith's Angels"},{"name":"University of Michigan Frankel Cardiovascular Center"},{"name":"University of Michigan Department of Cardiac Surgery"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08HL146351"],"award-info":[{"award-number":["K08HL146351"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002020","name":"Children's Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002020","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08HL146351"],"award-info":[{"award-number":["K08HL146351"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although mesenchymal stem\/stromal cells (MSCs) are being explored in numerous clinical trials as proangiogenic and proregenerative agents, the influence of tissue origin on the therapeutic qualities of these cells is poorly understood. Complicating the functional comparison of different types of MSCs are the confounding effects of donor age, genetic background, and health status of the donor. Leveraging a clinical setting where MSCs can be simultaneously isolated from discarded but healthy bone and thymus tissues from the same neonatal patients, thereby controlling for these confounding factors, we performed an in vitro and in vivo paired comparison of these cells. We found that both neonatal thymus (nt)MSCs and neonatal bone (nb)MSCs expressed different pericytic surface marker profiles. Further, ntMSCs were more potent in promoting angiogenesis in vitro and in vivo and they were also more motile and efficient at invading ECM in vitro. These functional differences were in part mediated by an increased ntMSC expression of SLIT3, a factor known to activate endothelial cells. Further, we discovered that SLIT3 stimulated MSC motility and fibrin gel invasion via ROBO1 in an autocrine fashion. Consistent with our findings in human MSCs, we found that SLIT3 and ROBO1 were expressed in the perivascular cells of the neonatal murine thymus gland and that global SLIT3 or ROBO1 deficiency resulted in decreased neonatal murine thymus gland vascular density. In conclusion, ntMSCs possess increased proangiogenic and invasive behaviors, which are in part mediated by the paracrine and autocrine effects of SLIT3.<\/jats:p>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Significance statement Mesenchymal stromal cells (MSCs), due to their ubiquity, can be isolated from various tissues and are being evaluated for their therapeutic effects. Despite their advanced clinical evaluation, the tissue-specific pro-regenerative properties of MSCs are poorly understood. Using a unique clinical situation that permits simultaneous isolation of thymus- and bone-derived MSCs from the same patient, a paired comparison was performed, which allowed to control for donor age, health status, and individual variability. It was found that neonatal thymus MSCs possess more proangiogenic, motile, and invasive behavior and that this is in part due to increased signaling from the SLIT3-ROBO1 axis. In sum, human MSCs likely have important tissue-specific regenerative characteristics and MSC SLIT3 expression may be an informative biomarker for regenerative and therapeutic potency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/sctm.19-0448","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T14:59:03Z","timestamp":1590764343000},"page":"1102-1113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Tissue-specific angiogenic and invasive properties of human neonatal thymus and bone MSCs: Role of SLIT3-ROBO1"],"prefix":"10.1093","volume":"9","author":[{"given":"Shuyun","family":"Wang","sequence":"first","affiliation":[{"name":"1 Department of Cardiac Surgery, Section of Pediatric Cardiovascular Surgery University of Michigan, Ann Arbor, Michigan, 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Surgery University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Colomb","sequence":"additional","affiliation":[{"name":"1 Department of Cardiac Surgery, Section of Pediatric Cardiovascular Surgery University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Witt","sequence":"additional","affiliation":[{"name":"2 Department of General Surgery Brigham and Women's Hospital, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Jaworski","sequence":"additional","affiliation":[{"name":"3 Department of Neuroscience Brown University, Providence, Rhode Island, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Weiss","sequence":"additional","affiliation":[{"name":"4 Department of Internal Medicine University of Michigan, Ann Arbor, Michigan, 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