{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T21:12:50Z","timestamp":1773868370128,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Investigator-initiated Projects","award":["05163296"],"award-info":[{"award-number":["05163296"]}]},{"name":"Chi Lin Kok Ng BHL Foundation","award":["05163296"],"award-info":[{"award-number":["05163296"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The in vitro derivation of Schwann cells from human bone marrow stromal cells (hBMSCs) opens avenues for autologous transplantation to achieve remyelination therapy for post-traumatic neural regeneration. Towards this end, we exploited human induced pluripotent stem-cell-derived sensory neurons to direct Schwann-cell-like cells derived from among the hBMSC-neurosphere cells into lineage-committed Schwann cells (hBMSC-dSCs). These cells were seeded into synthetic conduits for bridging critical gaps in a rat model of sciatic nerve injury. With improvement in gait by 12-week post-bridging, evoked signals were also detectable across the bridged nerve. Confocal microscopy revealed axially aligned axons in association with MBP-positive myelin layers across the bridge in contrast to null in non-seeded controls. Myelinating hBMSC-dSCs within the conduit were positive for both MBP and human nucleus marker HuN. We then implanted hBMSC-dSCs into the contused thoracic cord of rats. By 12-week post-implantation, significant improvement in hindlimb motor function was detectable if chondroitinase ABC was co-delivered to the injured site; such cord segments showed axons myelinated by hBMSC-dSCs. Results support translation into a protocol by which lineage-committed hBMSC-dSCs become available for motor function recovery after traumatic injury to both peripheral and central nervous systems.<\/jats:p>","DOI":"10.3390\/cells12111479","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T01:52:43Z","timestamp":1685065963000},"page":"1479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["IPSC-Derived Sensory Neurons Directing Fate Commitment of Human BMSC-Derived Schwann Cells: Applications in Traumatic Neural Injuries"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5054-6966","authenticated-orcid":false,"given":"Kin-Wai","family":"Tam","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheuk-Yin","family":"Wong","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3987-6830","authenticated-orcid":false,"given":"Kenneth Lap-Kei","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Lam","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotong","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wai-Ting","family":"Wong","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian Tak-Sui","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wing-Yui","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sa","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham Ka-Hon","family":"Shea","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisy Kwok-Yan","family":"Shum","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"},{"name":"State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6228-1595","authenticated-orcid":false,"given":"Ying-Shing","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"},{"name":"State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1113\/JP270874","article-title":"The repair Schwann cell and its function in regenerating nerves","volume":"594","author":"Jessen","year":"2016","journal-title":"J. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e62232","DOI":"10.7554\/eLife.62232","article-title":"Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun","volume":"10","author":"Wagstaff","year":"2021","journal-title":"eLife"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.biomaterials.2010.09.046","article-title":"The regeneration of transected sciatic nerves of adult rats using chitosan nerve conduits seeded with bone marrow stromal cell-derived Schwann cells","volume":"32","author":"Ao","year":"2011","journal-title":"Biomaterials"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1097\/NEN.0b013e3181eff6dc","article-title":"Human umbilical cord-derived mesenchymal stromal cells differentiate into functional Schwann cells that sustain peripheral nerve regeneration","volume":"69","author":"Matsuse","year":"2010","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"806","DOI":"10.3171\/jns.2004.101.5.0806","article-title":"Peripheral nerve regeneration by transplantation of bone marrow stromal cell-derived Schwann cells in adult rats","volume":"101","author":"Mimura","year":"2004","journal-title":"J. Neurosurg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/nn.4541","article-title":"Cell transplantation therapy for spinal cord injury","volume":"20","author":"Assinck","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1096\/fj.03-0196fje","article-title":"Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury","volume":"18","author":"Chau","year":"2004","journal-title":"FASEB J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12299","DOI":"10.1021\/acsami.7b00882","article-title":"Differentiation of bone marrow stem cells into Schwann cells for the promotion of neurite outgrowth on electrospun fibers","volume":"9","author":"Xue","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1901570","DOI":"10.1002\/adhm.201901570","article-title":"Electric conductivity on aligned nanofibers facilitates the transdifferentiation of mesenchymal stem cells into Schwann cells and regeneration of injured peripheral nerve","volume":"9","author":"Hu","year":"2020","journal-title":"Adv. Healthc. Mater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1479137","DOI":"10.1155\/2017\/1479137","article-title":"Maintenance of a Schwann-like phenotype in differentiated adipose-derived stem cells requires the synergistic action of multiple growth factors","volume":"2017","author":"Mortimer","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.expneurol.2010.05.005","article-title":"Bone marrow-derived Schwann cells achieve fate commitment\u2014A prerequisite for remyelination therapy","volume":"224","author":"Shea","year":"2010","journal-title":"Exp. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1111\/ejn.14837","article-title":"Juxtacrine signaling via Notch and ErbB receptors in the switch to fate commitment of bone marrow-derived Schwann cells","volume":"52","author":"Shea","year":"2020","journal-title":"Eur. J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.stemcr.2017.08.004","article-title":"Directed differentiation of human bone marrow stromal cells to fate-committed Schwann cells","volume":"9","author":"Cai","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.5966\/sctm.2015-0424","article-title":"Human induced pluripotent cell-derived sensory neurons for fate commitment of bone marrow-derived Schwann cells: Implications for remyelination therapy","volume":"6","author":"Cai","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.bbrc.2009.01.031","article-title":"Development of mesenchymal stem cells partially originate from the neural crest","volume":"379","author":"Morikawa","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","first-page":"3","article-title":"Isolation and culture of bone marrow-derived human multipotent stromal cells (hMSCs)","volume":"449","author":"Wolfe","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1097\/00006534-199612000-00023","article-title":"Sciatic function index, nerve conduction tests, muscle contraction, and axon morphometry as indicators of regeneration","volume":"98","author":"Kanaya","year":"1996","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/0014-4886(82)90234-5","article-title":"An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks","volume":"77","author":"Freed","year":"1982","journal-title":"Exp. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"829","DOI":"10.4103\/1673-5374.182712","article-title":"A self-made, low-cost infrared system for evaluating the sciatic functional index in mice","volume":"11","author":"Fricker","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.expneurol.2009.06.012","article-title":"Bilateral cervical contusion spinal cord injury in rats","volume":"220","author":"Anderson","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3344\/kjp.2019.32.1.12","article-title":"Animals models of spinal cord contusion injury","volume":"32","author":"Verma","year":"2019","journal-title":"Korean J. Pain."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/neu.1995.12.1","article-title":"A sensitive and reliable locomotor rating scale for open field testing in rats","volume":"12","author":"Basso","year":"1995","journal-title":"J. Neurotrauma."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0165-0270(02)00012-2","article-title":"Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: A new task to evaluate fore- and hindlimb stepping, placing, and co-ordination","volume":"115","author":"Metz","year":"2002","journal-title":"J. Neurosci. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/glia.23047","article-title":"Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface","volume":"65","author":"Lindsay","year":"2017","journal-title":"Glia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11262","DOI":"10.1038\/s41598-020-67526-0","article-title":"Secretion of a mammalian chondroitinase ABC aids glial integration at PNS\/CNS boundaries","volume":"10","author":"Warren","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mcn.2004.06.010","article-title":"The role of proteoglycans in Schwann cell\/astrocyte interactions and in regeneration failure at PNS\/CNS interfaces","volume":"28","author":"Grimpe","year":"2005","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nrn1746","article-title":"The origin and development of glial cells in peripheral nerves","volume":"6","author":"Jessen","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1006\/exnr.2001.7846","article-title":"Effect of allogeneic Schwann cell transplantation on peripheral nerve regeneration","volume":"173","author":"Mosahebi","year":"2002","journal-title":"Exp. Neurol."},{"key":"ref_29","first-page":"152","article-title":"Functional, histopathological and immunohistochemical assessments of cyclosporine A on sciatic nerve regeneration using allografts: A rat sciatic nerve model","volume":"5","author":"Amniattalab","year":"2017","journal-title":"Bull. Emerg. Trauma."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/(SICI)1097-4598(199912)22:12<1631::AID-MUS3>3.0.CO;2-V","article-title":"Muscle disorders associated with cyclosporine treatment","volume":"22","author":"Breil","year":"1999","journal-title":"Muscle Nerve"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/0022-510X(92)90146-C","article-title":"Immunosuppression in nerve allografting: Is it desirable?","volume":"112","author":"Ansselin","year":"1992","journal-title":"J. Neurol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1089\/ten.teb.2020.0355","article-title":"Three-dimensional engineered peripheral nerve: Toward a new era of patient-specific nerve repair solutions","volume":"28","author":"Selim","year":"2022","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3389\/fncel.2019.00033","article-title":"The success and failure of the Schwann cell response to nerve injury","volume":"13","author":"Jessen","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/(SICI)1098-2752(1998)18:7<397::AID-MICR2>3.0.CO;2-F","article-title":"Schwann cells, neurotrophic factors, and peripheral nerve regeneration","volume":"18","author":"Frostick","year":"1998","journal-title":"Microsurgery"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4703","DOI":"10.1096\/fj.201801799R","article-title":"Secretome analysis of nerve repair mediating Schwann cells reveals Smad-dependent trophism","volume":"33","author":"Schira","year":"2019","journal-title":"FASEB J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/j.1365-2990.1990.tb01277.x","article-title":"The role of Schwann cells and basal lamina tubes in the regeneration of axons through long lengths of freeze-killed nerve grafts","volume":"16","author":"Nadim","year":"1990","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3389\/fbioe.2019.00337","article-title":"Modern trends for peripheral nerve repair and regeneration: Beyond the hollow nerve guidance conduit","volume":"7","author":"Carvalho","year":"2019","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/micr.1920100316","article-title":"Sciatic nerve regeneration in the rat. Validity of walking track assessment in the presence of chronic contractures","volume":"10","author":"Dellon","year":"1989","journal-title":"Microsurgery"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/11\/1479\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:42:18Z","timestamp":1760125338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/11\/1479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,25]]},"references-count":38,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["cells12111479"],"URL":"https:\/\/doi.org\/10.3390\/cells12111479","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,25]]}}}