{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:51:44Z","timestamp":1778028704196,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["2 R01 NS051706"],"award-info":[{"award-number":["2 R01 NS051706"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007930","name":"Institute of Clinical and Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR000448"],"award-info":[{"award-number":["UL1 TR000448"]}],"id":[{"id":"10.13039\/100007930","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotech &amp;amp; Bioengineering"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Providing temporally regulated glial cell line\u2010derived neurotrophic factor (GDNF) to injured nerve can promote robust axon regeneration. However, it is poorly understood why providing highly elevated levels of GDNF to nerve can lead to axon entrapment in the zone containing elevated GDNF. This limited understanding represents an obstacle to the translation of GDNF therapies to treat nerve injuries clinically. Here, we investigated how transgenic Schwann cells (SCs) overexpressing GDNF\u2010IRES\u2010DsRed impact nerve regeneration. Cultured primary SCs were transduced with lentiviruses (GDNF\u2010overexpressing transgenic SCs), one of which provides the capability to express high levels of GDNF and regulate temporal GDNF expression. These SC groups were transplanted into acellular nerve allografts (ANAs) bridging a 14\u2009mm rat sciatic nerve defect. GDNF\u2010overexpressing transgenic SCs expressing GDNF for as little as 1\u2009week decreased axon regeneration across ANAs and caused extensive extracellular matrix (ECM) remodeling. To determine whether additional gene expression changes beyond GDNF transgene expression occurred in GDNF\u2010overexpressing transgenic SCs, microarray analysis of GDNF\u2010overexpressing transgenic SCs compared to untreated SCs was performed. Microarray analysis revealed a set of common genes regulated in transgenic SC groups expressing high levels of GDNF compared to untreated SCs. A co\u2010culture model of GDNF\u2010overexpressing transgenic SCs with fibroblasts (FBs) revealed differential FB ECM\u2010related gene expression compared to untreated SCs. These data suggest a component of axon entrapment is independent of GDNF's impact on axons. Biotechnol. Bioeng. 2017;114: 2121\u20132130. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bit.26335","type":"journal-article","created":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T07:12:45Z","timestamp":1494227565000},"page":"2121-2130","source":"Crossref","is-referenced-by-count":18,"title":["Transgenic SCs expressing GDNF\u2010IRES\u2010DsRed impair nerve regeneration within acellular nerve allografts"],"prefix":"10.1002","volume":"114","author":[{"given":"Xueping","family":"Ee","sequence":"first","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery Washington University School of Medicine Campus Box 8238, 660 South Euclid Avenue St. Louis Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Yan","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery Washington University School of Medicine Campus Box 8238, 660 South Euclid Avenue St. Louis Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery Washington University School of Medicine Campus Box 8238, 660 South Euclid Avenue St. Louis Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Schellhardt","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery Washington University School of Medicine Campus Box 8238, 660 South Euclid Avenue St. Louis Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelly E.","family":"Sakiyama\u2010Elbert","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery Washington University School of Medicine Campus Box 8238, 660 South Euclid Avenue St. Louis Missouri 63110"},{"name":"Department of Biomedical Engineering Washington University St. Louis Missouri"},{"name":"Department of Biomedical Engineering The University of Texas at Austin Austin Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Mackinnon","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery Washington University School of Medicine Campus Box 8238, 660 South Euclid Avenue St. Louis Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8132-6827","authenticated-orcid":false,"given":"Matthew D.","family":"Wood","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery Washington University School of Medicine Campus Box 8238, 660 South Euclid Avenue St. Louis Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,5,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-08-03059.1998"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00183-3"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1385\/MN:27:3:277"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.04.057"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071076"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2008.05.018"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M213066200"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-05-03876.1995"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-05-03886.1995"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02740621"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00756.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6156-10.2011"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.12.1873"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59320"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200006050-00011"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2001.7826"},{"issue":"2","key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1523\/JNEUROSCI.23-02-00561.2003","article-title":"Glial cell line\u2010derived neurotrophic factor alters axon schwann cell units and promotes myelination in unmyelinated nerve fibers","volume":"23","author":"Hoke A","year":"2003","journal-title":"J Neurosci"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2015.00032"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753193411420348"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2007.06.018"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03290.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.04.005"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10353-013-0205-0"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.118"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19970715)49:2<236::AID-JNR12>3.0.CO;2-Z"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(03)00326-7"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.137.2.481"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199707)20:7<858::AID-MUS10>3.0.CO;2-O"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00383.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5089-06.2007"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1055\/b-003-106416"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2015.0311"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2013.05.006"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.12.003"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(199701)32:1<22::AID-NEU3>3.0.CO;2-G"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.1038"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.112.3.457"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-08-02433.1991"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1997.tb01499.x"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2016.0003"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687785"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23490"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2013.10.004"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1264"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06452.x"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0553"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.130.1.137"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.04963.x"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1998.70020531.x"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24800"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.2217\/rme.12.105"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25247"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbit.26335","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.26335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T15:41:27Z","timestamp":1759938087000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.26335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,18]]},"references-count":52,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1002\/bit.26335"],"URL":"https:\/\/doi.org\/10.1002\/bit.26335","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,18]]}}}