{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T04:50:53Z","timestamp":1749185453896},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation: Stiftung Tumorforschung Kopf-Hals, Wiesbaden","award":["16.11.2020"],"award-info":[{"award-number":["16.11.2020"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Inducing axial vascularisation of tissue engineering constructs is a well-established method to support tissue growth in large 3-dimensional tissues. Progenitor cell chemotaxis towards axially vascularized tissues has not been well characterized. In a prospective randomized controlled study including 32 male syngeneic Lewis rats we investigated the capability of the axially vascularized constructs to attract systemically injected bone marrow mononuclear cells (BMMNCs). The underlying mechanism for cell homing was investigated focusing on the role of hypoxia and the SDF1-CXCR4-7 axis. Sixteen animals were used as donors for BMMNCs. The other animals were subjected to implantation of a tissue engineering construct in the subcutaneous groin region. These constructs were axially vascularized either via an arteriovenous loop (AVL, n = 6) or via uninterrupted flow-through vessels (non-AVL, n = 10). BMMNCs were labelled with quantum dots (Qdot\u00ae 655) and injected 12 days after surgery either via intra-arterial or intravenous routes. 2 days after cell injection, the animals were sacrificed and examined using fluorescence microscopy. The Qdot\u00ae 655 signals were detected exclusively in the liver, spleen, AVL constructs and to a minimal extent in the non-AVL constructs. A significant difference could be detected between the number of labelled cells in the AVL and non-AVL constructs with more cells detected in the AVL constructs specially in central zones (<jats:italic>p<\/jats:italic> &lt;0.0001). The immunohistological analysis showed a significant increase in the absolute expression of HIF-1 in the AVL group in comparison to the non-AVL group. The PCR analysis confirmed a 1.4-fold increase in HIF-1 expression in AVL constructs. Although PCR analysis showed an enhanced expression of CXCR4 and CXCR7 in AVL constructs, no significant differences in SDF1 expression were detected via immunohistological or PCR analysis. At the examined time point, the AVL constructs can attract BMMNCs in a mechanism probably related to the hypoxia associated with a robust tissue formation.<\/jats:p>","DOI":"10.1371\/journal.pone.0272697","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T17:33:44Z","timestamp":1660239224000},"page":"e0272697","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Systemically injected bone marrow mononuclear cells specifically home to axially vascularized tissue engineering constructs"],"prefix":"10.1371","volume":"17","author":[{"given":"Ahmad","family":"Eweida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia","family":"Flechtenmacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elli","family":"Sandberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Schulte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker J.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Kneser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Harhaus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"pone.0272697.ref001","doi-asserted-by":"crossref","first-page":"448","DOI":"10.3389\/fbioe.2019.00448","article-title":"Convergence of Scaffold-Guided Bone Reconstruction and Surgical Vascularization Strategies-A Quest for Regenerative Matching Axial Vascularization","volume":"7","author":"DS Sparks","year":"2019","journal-title":"Front Bioeng Biotechnol"},{"issue":"3\u20134","key":"pone.0272697.ref002","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1159\/000492417","article-title":"The Arteriovenous Loop: Engineering of Axially Vascularized Tissue","volume":"59","author":"A Weigand","year":"2018","journal-title":"Eur Surg Res"},{"key":"pone.0272697.ref003","first-page":"530","article-title":"New capillary bed formation with a surgically constructed arteriovenous fistula","volume":"30","author":"OO Erol","year":"1979","journal-title":"Surg Forum"},{"issue":"2","key":"pone.0272697.ref004","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1096\/fj.06-6614com","article-title":"An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct","volume":"21","author":"Z Lokmic","year":"2007","journal-title":"FASEB J"},{"issue":"7","key":"pone.0272697.ref005","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1111\/jcmm.12296","article-title":"Successful human long-term application of in situ bone tissue engineering","volume":"18","author":"RE Horch","year":"2014","journal-title":"J Cell Mol Med"},{"issue":"7","key":"pone.0272697.ref006","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.jcms.2014.10.018","article-title":"Axially vascularised mandibular constructs: Is it time for a clinical trial?","volume":"43","author":"AM Eweida","year":"2015","journal-title":"J Craniomaxillofac Surg"},{"key":"pone.0272697.ref007","article-title":"Mandibular Reconstruction Using Tissue Regeneration With Axially Vascularised Bone Substitutes","author":"A. Eweida","year":"2019","journal-title":"Alexandria, Egypt"},{"issue":"1","key":"pone.0272697.ref008","doi-asserted-by":"crossref","first-page":"e0117407","DOI":"10.1371\/journal.pone.0117407","article-title":"Flow increase is decisive to initiate angiogenesis in veins exposed to altered hemodynamics","volume":"10","author":"VJ Schmidt","year":"2015","journal-title":"PLoS One"},{"issue":"9\u201310","key":"pone.0272697.ref009","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1089\/ten.tea.2017.0262","article-title":"Vascularization of the Arteriovenous Loop in a Rat Isolation Chamber Model-Quantification of Hypoxia and Evaluation of Its Effects","volume":"24","author":"Q Yuan","year":"2018","journal-title":"Tissue Eng Part A"},{"issue":"2","key":"pone.0272697.ref010","doi-asserted-by":"crossref","first-page":"e657","DOI":"10.1002\/term.2336","article-title":"Axially vascularized tissue-engineered bone constructs retain their in vivo angiogenic and osteogenic capacity after high-dose irradiation","volume":"12","author":"A Eweida","year":"2018","journal-title":"J Tissue Eng Regen Med"},{"issue":"1","key":"pone.0272697.ref011","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13287-019-1238-5","article-title":"Safety and efficacy of bone marrow-derived cells therapy on cardiomyopathy: a meta-analysis","volume":"10","author":"C Wang","year":"2019","journal-title":"Stem Cell Res Ther"},{"issue":"6","key":"pone.0272697.ref012","doi-asserted-by":"crossref","first-page":"833","DOI":"10.2217\/rme.12.82","article-title":"Stem cell recruitment after injury: lessons for regenerative medicine","volume":"7","author":"RC Rennert","year":"2012","journal-title":"Regen Med"},{"issue":"3","key":"pone.0272697.ref013","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1097\/PCC.0000000000000324","article-title":"Autologous bone marrow mononuclear cells reduce therapeutic intensity for severe traumatic brain injury in children","volume":"16","author":"GP Liao","year":"2015","journal-title":"Pediatr Crit Care Med"},{"key":"pone.0272697.ref014","first-page":"732742","article-title":"MSCs: Delivery Routes and Engraftment, Cell-Targeting Strategies, and Immune Modulation","volume":"2013","author":"TJ Kean","year":"2013","journal-title":"Stem Cells Int"},{"issue":"8","key":"pone.0272697.ref015","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/nm1075","article-title":"Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1","volume":"10","author":"DJ Ceradini","year":"2004","journal-title":"Nat Med"},{"key":"pone.0272697.ref016","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.cyto.2017.12.022","article-title":"Multisystem multitasking by CXCL12 and its receptors CXCR4 and ACKR3","volume":"109","author":"PM Murphy","year":"2018","journal-title":"Cytokine"},{"key":"pone.0272697.ref017","first-page":"77","article-title":"Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g","volume":"97","author":"A. Boyum","year":"1968","journal-title":"Scand J Clin Lab Invest Suppl"},{"key":"pone.0272697.ref018","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1477-3155-5-9","article-title":"Quantum dot labeling of mesenchymal stem cells","volume":"5","author":"BJ Muller-Borer","year":"2007","journal-title":"J Nanobiotechnology"},{"key":"pone.0272697.ref019","doi-asserted-by":"crossref","first-page":"975871","DOI":"10.1155\/2012\/975871","article-title":"Markers for characterization of bone marrow multipotential stromal cells","volume":"2012","author":"SA Boxall","year":"2012","journal-title":"Stem Cells Int"},{"issue":"7","key":"pone.0272697.ref020","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1089\/ten.2006.12.1721","article-title":"Engineering of vascularized transplantable bone tissues: induction of axial vascularization in an osteoconductive matrix using an arteriovenous loop","volume":"12","author":"U Kneser","year":"2006","journal-title":"Tissue Eng"},{"issue":"9","key":"pone.0272697.ref021","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s00402-012-1550-3","article-title":"Axially vascularized bone substitutes: a systematic review of literature and presentation of a novel model","volume":"132","author":"AM Eweida","year":"2012","journal-title":"Arch Orthop Trauma Surg"},{"issue":"6","key":"pone.0272697.ref022","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1097\/01.PRS.0000086140.49022.AB","article-title":"Tissue engineering skin flaps: which vascular carrier, arteriovenous shunt loop or arteriovenous bundle, has more potential for angiogenesis and tissue generation?","volume":"112","author":"Y Tanaka","year":"2003","journal-title":"Plast Reconstr Surg"},{"issue":"1","key":"pone.0272697.ref023","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mvr.2007.04.003","article-title":"The venous graft as an effector of early angiogenesis in a fibrin matrix","volume":"75","author":"E Polykandriotis","year":"2008","journal-title":"Microvasc Res"},{"issue":"5","key":"pone.0272697.ref024","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1089\/scd.2008.0253","article-title":"Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect","volume":"18","author":"UM Fischer","year":"2009","journal-title":"Stem Cells Dev"},{"issue":"10","key":"pone.0272697.ref025","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.3324\/haematol.12553","article-title":"Factors that influence short-term homing of human bone marrow-derived mesenchymal stem cells in a xenogeneic animal model","volume":"93","author":"C Kyriakou","year":"2008","journal-title":"Haematologica"},{"issue":"1","key":"pone.0272697.ref026","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000047856","article-title":"The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion","volume":"169","author":"J Gao","year":"2001","journal-title":"Cells Tissues Organs"},{"issue":"8","key":"pone.0272697.ref027","first-page":"1295","article-title":"Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction","volume":"47","author":"WJ Kang","year":"2006","journal-title":"J Nucl Med"},{"issue":"8","key":"pone.0272697.ref028","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.bjps.2005.04.033","article-title":"The use of pimonidazole to characterise hypoxia in the internal environment of an in vivo tissue engineering chamber","volume":"58","author":"SO Hofer","year":"2005","journal-title":"Br J Plast Surg"},{"key":"pone.0272697.ref029","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12896-014-0112-x","article-title":"PHDs inhibitor DMOG promotes the vascularization process in the AV loop by HIF-1a up-regulation and the preliminary discussion on its kinetics in rat","volume":"14","author":"Q Yuan","year":"2014","journal-title":"BMC Biotechnol"},{"issue":"2","key":"pone.0272697.ref030","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1055\/s-0037-1607322","article-title":"Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs","volume":"34","author":"A Eweida","year":"2018","journal-title":"J Reconstr Microsurg"},{"issue":"5\u20136","key":"pone.0272697.ref031","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1159\/000493162","article-title":"Oxygen Regulation in Development: Lessons from Embryogenesis towards Tissue Engineering","volume":"205","author":"S Fathollahipour","year":"2018","journal-title":"Cells Tissues Organs"},{"issue":"3","key":"pone.0272697.ref032","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1089\/ten.tea.2007.0438","article-title":"Endothelial precursor cells home to a vascularized tissue engineering chamber by application of the angiogenic chemokine CXCL12","volume":"15","author":"JW Simcock","year":"2009","journal-title":"Tissue Eng Part A"},{"issue":"8","key":"pone.0272697.ref033","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1182\/blood-2004-03-1109","article-title":"Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues","volume":"104","author":"C Murdoch","year":"2004","journal-title":"Blood"},{"issue":"1","key":"pone.0272697.ref034","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00662.2006","article-title":"Biology of bone marrow-derived endothelial cell precursors","volume":"292","author":"GC Schatteman","year":"2007","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"16","key":"pone.0272697.ref035","doi-asserted-by":"crossref","first-page":"4376","DOI":"10.1182\/blood-2010-07-295964","article-title":"COMP-Ang1 stimulates HIF-1alpha-mediated SDF-1 overexpression and recovers ischemic injury through BM-derived progenitor cell recruitment","volume":"117","author":"SW Youn","year":"2011","journal-title":"Blood"},{"issue":"1","key":"pone.0272697.ref036","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1021\/bc034153y","article-title":"Noninvasive imaging of quantum dots in mice","volume":"15","author":"B Ballou","year":"2004","journal-title":"Bioconjug Chem"},{"issue":"7","key":"pone.0272697.ref037","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1007\/s11356-012-1457-0","article-title":"Stability of core\/shell quantum dots\u2014role of pH and small organic ligands","volume":"20","author":"RF Domingos","year":"2013","journal-title":"Environ Sci Pollut Res Int"},{"key":"pone.0272697.ref038","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1477-3155-8-13","article-title":"Dynamics and mechanisms of quantum dot nanoparticle cellular uptake","volume":"8","author":"Y Xiao","year":"2010","journal-title":"J Nanobiotechnology"},{"key":"pone.0272697.ref039","first-page":"2437","article-title":"Quantum dots affect expression of CD133 surface antigen in melanoma cells","volume":"6","author":"S Steponkiene","year":"2011","journal-title":"Int J Nanomedicine"},{"issue":"3","key":"pone.0272697.ref040","doi-asserted-by":"crossref","first-page":"e32650","DOI":"10.1371\/journal.pone.0032650","article-title":"Quantum dots do not affect the behaviour of mouse embryonic stem cells and kidney stem cells and are suitable for short-term tracking","volume":"7","author":"A Rak-Raszewska","year":"2012","journal-title":"PLoS One"},{"issue":"8","key":"pone.0272697.ref041","doi-asserted-by":"crossref","first-page":"e69182","DOI":"10.1371\/journal.pone.0069182","article-title":"Radiation therapy-induced tumor invasiveness is associated with SDF-1-regulated macrophage mobilization and vasculogenesis","volume":"8","author":"SC Wang","year":"2013","journal-title":"PLoS One"},{"issue":"2","key":"pone.0272697.ref042","first-page":"469","article-title":"Cancer stem cells and hypoxia-inducible factors (Review)","volume":"53","author":"WW Tong","year":"2018","journal-title":"Int J Oncol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0272697","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T17:34:37Z","timestamp":1660239277000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0272697"}},"subtitle":[],"editor":[{"given":"Dhermendra","family":"Tiwari","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,8,11]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0272697","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,11]]}}}