Safety of intramedullary Schwann cell transplantation for postrehabilitation spinal cord injuries: 2-year follow-up of 33 cases

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Many experimental studies on spinal cord injuries (SCIs) support behavioral improvement after Schwann cell treatment. This study was conducted to evaluate safety issues 2 years after intramedullary Schwann cell transplantation in 33 consecutively selected patients with SCI.


Of 356 patients with SCIs who had completed at least 6 months of a conventional rehabilitation program and who were screened for the study criteria, 33 were enrolled. After giving their informed consent, they volunteered for participation. They underwent sural nerve harvesting and intramedullary injection of a processed Schwann cell solution. Outcome assessments included a general health questionnaire, neurological examination, and functional recordings in terms of American Spinal Injury Association (ASIA) and Functional Independence Measure scoring, which were documented by independent observers. There were 24 patients with thoracic and 9 with cervical injuries. Sixteen patients were categorized in ASIA Grade A, and the 17 remaining participants had ASIA Grade B.


There were no cases of deep infection, and the follow-up MR imaging studies obtained at 2 years did not reveal any deformity related to the procedure. There was no case of permanent neurological worsening or any infectious or viral complications. No new increment in syrinx size or abnormal tissue and/or tumor formation were observed on contrast-enhanced MR imaging studies performed 2 years after the treatment.


Preliminary results, especially in terms of safety, seem to be promising, paving the way for future cell therapy trials.

Abbreviations used in this paper: ASIA = American Spinal Injury Association; FAM = Functional Assessment Measure; FIM = Functional Independence Measure; SCI = spinal cord injury.

Article Information

Address correspondence to: Hooshang Saberi, M.D., M.P.H., Department of Neurosurgery, Brain and Spinal Injuries Repair Research Center, Tehran University of Medical Sciences, Imam Khomeini Hospital, Keshavarz Boulevard, Tehran 14197, Iran. email: (cc:

Please include this information when citing this paper: published online July 29, 2011; DOI: 10.3171/2011.6.SPINE10917.

© AANS, except where prohibited by US copyright law.



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    T2-weighted MR imaging study obtained in a patient with C-6 SCI. Note the hyperintense region at the fracture site approximately 14 mm rostrocaudally; there is minimal cord compression.

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    A: Inverted microscope view of spindle-shaped cell culture. Original magnification × 4. B: Cultured cells stained with S100, showing highly positive staining. Original magnification × 10. C: Electron microscopic view of the cultured cells, demonstrating large cytoplasmic extensions.

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    Intraoperative photograph (D) of the spinal cord at the lesion level. The lesion was exposed after laminectomy and durotomy under imaging guidance in coronal (A), sagittal (B), and axial (C) planes.



Agudo MWoodhoo AWebber DMirsky RJessen KRMcMahon SB: Schwann cell precursors transplanted into the injured spinal cord multiply, integrate and are permissive for axon growth. Glia 56:126312702008


Ao QWang AJChen GQWang SJZuo HCZhang XF: Combined transplantation of neural stem cells and olfactory ensheathing cells for the repair of spinal cord injuries. Med Hypotheses 69:123412372007


Au ERichter MWVincent AJTetzlaff WAebersold RSage EH: SPARC from olfactory ensheathing cells stimulates Schwann cells to promote neurite outgrowth and enhances spinal cord repair. J Neurosci 27:720872212007


Bachelin CLachapelle FGirard CMoissonnier PSerguera-Lagache CMallet J: Efficient myelin repair in the macaque spinal cord by autologous grafts of Schwann cells. Brain 128:5405492005


Ban De XKong XHFeng SQNing GZChen JTGuo SF: Intraspinal cord graft of autologous activated Schwann cells efficiently promotes axonal regeneration and functional recovery after rat's spinal cord injury. Brain Res 1256:1491612009


Baptiste DCFehlings MG: Update on the treatment of spinal cord injury. Prog Brain Res 161:2172332007


Barakat DJGaglani SMNeravetla SRSanchez ARAndrade CMPressman Y: Survival, integration, and axon growth support of glia transplanted into the chronically contused spinal cord. Cell Transplant 14:2252402005


Bartolomei JCGreer CA: Olfactory ensheathing cells: bridging the gap in spinal cord injury. Neurosurgery 47:105710692000


Ben-Hur TGoldman SA: Prospects of cell therapy for disorders of myelin. Ann N Y Acad Sci 1142:2182492008


Bentley CALee KF: p75 is important for axon growth and schwann cell migration during development. J Neurosci 20:770677152000


Bilginer BOnal MBNarin FUstun HKilinc KAkalan N: Antiapoptotic and neuroprotective effects of mycophenolate mofetil after acute spinal cord injury in young rats. Childs Nerv Syst 25:155515612009


Blight ACurt ADitunno JFDobkin BEllaway PFawcett J: Position statement on the sale of unproven cellular therapies for spinal cord injury: the international campaign for cures of spinal cord injury paralysis. Spinal Cord 47:7137142009


Buchet DBaron-Van Evercooren A: In search of human oligodendroglia for myelin repair. Neurosci Lett 456:1121192009


Bunge MB: Novel combination strategies to repair the injured mammalian spinal cord. J Spinal Cord Med 31:2622692008


Bunge MBPearse DD: Transplantation strategies to promote repair of the injured spinal cord. J Rehabil Res Dev 40:4 Suppl 155622003


Callera Fdo Nascimento RX: Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury: a preliminary safety study. Exp Hematol 34:1301312006


Catz AItzkovich M: Spinal Cord Independence Measure: comprehensive ability rating scale for the spinal cord lesion patient. J Rehabil Res Dev 44:65682007


Chau CHShum DKLi HPei JLui YYWirthlin L: Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury. FASEB J 18:1941962003


Chen AXu XMKleitman NBunge MB: Methylprednisolone administration improves axonal regeneration into Schwann cell grafts in transected adult rat thoracic spinal cord. Exp Neurol 138:2612761996


Chhabra HSLima CSachdeva SMittal ANigam VChaturvedi D: Autologous olfactory [corrected] mucosal transplant in chronic spinal cord injury: an Indian Pilot Study. Spinal Cord 47:8878952009


Compagnone NA: Treatments for spinal cord injury: is there hope in neurosteroids?. J Steroid Biochem Mol Biol 109:3073132008


Courtine GGerasimenko Yvan den Brand RYew AMusienko PZhong H: Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci 12:133313422009


Curt ADietz V: Controversial treatments for spinal-cord injuries. Lancet 365:8412005


Dezawa MMutoh TDezawa AAdachi-Usami E: Putative gap junctional communication between axon and regenerating Schwann cells during mammalian peripheral nerve regeneration. Neuroscience 85:6636671998


Dinh PBhatia NRasouli ASuryadevara SCahill KGupta R: Transplantation of preconditioned Schwann cells following hemisection spinal cord injury. Spine (Phila Pa 1976) 32:9439492007


Dobkin BHCurt AGuest J: Cellular transplants in China: observational study from the largest human experiment in chronic spinal cord injury. Neurorehabil Neural Repair 20:5132006


Domeniconi MFilbin MT: Overcoming inhibitors in myelin to promote axonal regeneration. J Neurol Sci 233:43472005


Eftekharpour EKarimi-Abdolrezaee SFehlings MG: Current status of experimental cell replacement approaches to spinal cord injury. Neurosurg Focus 24:3–4E192008


Farin ALiu CYLangmoen IAApuzzo ML: Biological restoration of central nervous system architecture and function: part 3-stem cell- and cell-based applications and realities in the biological management of central nervous system disorders: traumatic, vascular, and epilepsy disorders. Neurosurgery 65:8318592009


Fawcett JWCurt ASteeves JDColeman WPTuszynski MHLammertse D: Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. Spinal Cord 45:1902052007


Fehlings MGBaptiste DC: Current status of clinical trials for acute spinal cord injury. Injury 36:Suppl 2B113B1222005


Féron FPerry CCochrane JLicina PNowitzke AUrquhart S: Autologous olfactory ensheathing cell transplantation in human spinal cord injury. Brain 128:295129602005


Filbin MT: Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat Rev Neurosci 4:7037132003


Firouzi MMoshayedi PSaberi HMobasheri HAbolhassani FJahanzad I: Transplantation of Schwann cells to subarachnoid space induces repair in contused rat spinal cord. Neurosci Lett 402:66702006


Fortun JHill CEBunge MB: Combinatorial strategies with Schwann cell transplantation to improve repair of the injured spinal cord. Neurosci Lett 456:1241322009


Fouad KSchnell LBunge MBSchwab MELiebscher TPearse DD: Combining Schwann cell bridges and olfactory-ensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal cord. J Neurosci 25:116911782005


Franssen EHDe Bree FMEssing AHRamon-Cueto AVerhaagen J: Comparative gene expression profiling of olfactory ensheathing glia and Schwann cells indicates distinct tissue repair characteristics of olfactory ensheathing glia. Glia 56:128512982008


Franssen EHde Bree FMVerhaagen J: Olfactory ensheathing glia: their contribution to primary olfactory nervous system regeneration and their regenerative potential following transplantation into the injured spinal cord. Brain Res Rev 56:2362582007


García-Alías GLópez-Vales RForés JNavarro XVerdú E: Acute transplantation of olfactory ensheathing cells or Schwann cells promotes recovery after spinal cord injury in the rat. J Neurosci Res 75:6326412004


Gilson JMBlakemore WF: Schwann cell remyelination is not replaced by oligodendrocyte remyelination following ethidium bromide induced demyelination. Neuroreport 13:120512082002


Golden KLPearse DDBlits BGarg MSOudega MWood PM: Transduced Schwann cells promote axon growth and myelination after spinal cord injury. Exp Neurol 207:2032172007


Grimpe BPressman YLupa MDHorn KPBunge MBSilver J: The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces. Mol Cell Neurosci 28:18292005


Guest JDRao AOlson LBunge MBBunge RP: The ability of human Schwann cell grafts to promote regeneration in the transected nude rat spinal cord. Exp Neurol 148:5025221997


Hawryluk GWRowland JKwon BKFehlings MG: Protection and repair of the injured spinal cord: a review of completed, ongoing, and planned clinical trials for acute spinal cord injury. Neurosurg Focus 25:5E142008


Hill CEHurtado ABlits BBahr BAWood PMBartlett Bunge M: Early necrosis and apoptosis of Schwann cells transplanted into the injured rat spinal cord. Eur J Neurosci 26:143314452007


Hill CEMoon LDWood PMBunge MB: Labeled Schwann cell transplantation: cell loss, host Schwann cell replacement, and strategies to enhance survival. Glia 53:3383432006


Honmou OFelts PAWaxman SGKocsis JD: Restoration of normal conduction properties in demyelinated spinal cord axons in the adult rat by transplantation of exogenous Schwann cells. J Neurosci 16:319932081996


Huang HChen LWang HXi HGou CZhang J: Safety of fetal olfactory ensheathing cell transplantation in patients with chronic spinal cord injury. A 38-month follow-up with MRI. Zhonqquo Xiu Fu Chong Jian Wai Ke Za Zhi 20:4394432006


Ito YSugimoto YTomioka MKai NTanaka M: Does high dose methylprednisolone sodium succinate really improve neurological status in patient with acute cervical cord injury? : a prospective study about neurological recovery and early complications. Spine (Phila Pa 1976) 34:212121242009


Iwashita YFawcett JWCrang AJFranklin RJBlakemore WF: Schwann cells transplanted into normal and X-irradiated adult white matter do not migrate extensively and show poor long-term survival. Exp Neurol 164:2923022000


Jacobs WBFehlings MG: The molecular basis of neural regeneration. Neurosurgery 53:9439502003


Jasmin LJanni GMoallem TMLappi DAOhara PT: Schwann cells are removed from the spinal cord after effecting recovery from paraplegia. J Neurosci 20:921592232000


Keirstead HSMorgan SVWilby MJFawcett JW: Enhanced axonal regeneration following combined demyelination plus schwann cell transplantation therapy in the injured adult spinal cord. Exp Neurol 159:2252361999


King VRAlovskaya AWei DYBrown RAPriestley JV: The use of injectable forms of fibrin and fibronectin to support axonal ingrowth after spinal cord injury. Biomaterials 31:444744562010


Knoller NAuerbach GFulga VZelig GAttias JBakimer R: Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine 3:1731812005


Kocsis JDLankford KLSasaki MRadtke C: Unique in vivo properties of olfactory ensheathing cells that may contribute to neural repair and protection following spinal cord injury. Neurosci Lett 456:1371422009


Koda MSomeya YNishio YKadota RMannoji CMiyashita T: Brain-derived neurotrophic factor suppresses anoikis-induced death of Schwann cells. Neurosci Lett 444:1431472008


Kumar AAKumar SRNarayanan RArul KBaskaran M: Autologous bone marrow derived mononuclear cell therapy for spinal cord injury: a phase I/II clinical safety and primary efficacy data. Exp Clin Transplant 7:2412482009


Lakatos ABarnett SCFranklin RJ: Olfactory ensheathing cells induce less host astrocyte response and chondroitin sulphate proteoglycan expression than Schwann cells following transplantation into adult CNS white matter. Exp Neurol 184:2372462003


Lammertse DTuszynski MHSteeves JDCurt AFawcett JWRask C: Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design. Spinal Cord 45:2322422007


Lankford KLImaizumi THonmou OKocsis JD: A quantitative morphometric analysis of rat spinal cord remyelination following transplantation of allogenic Schwann cells. J Comp Neurol 443:2592742002


Lavdas AAMatsas R: Towards personalized cell-replacement therapies for brain repair. Per Med 6:2933132009


Lavdas AAPapastefanaki FThomaidou DMatsas R: Schwann cell transplantation for CNS repair. Curr Med Chem 15:1511602008


Li YChopp M: Marrow stromal cell transplantation in stroke and traumatic brain injury. Neurosci Lett 456:1201232009


Li YRaisman G: Schwann cells induce sprouting in motor and sensory axons in the adult rat spinal cord. J Neurosci 14:405040631994


Lima CEscada PPratas-Vital JBranco CArcangeli CALazzeri G: Olfactory mucosal autografts and rehabilitation for chronic traumatic spinal cord injury. Neurorehabil Neural Repair 24:10222010


Lima CPratas-Vital JEscada PHasse-Ferreira ACapucho CPeduzzi JD: Olfactory mucosa autografts in human spinal cord injury: a pilot clinical study. J Spinal Cord Med 29:1912062006


Mackay-Sim A: Olfactory ensheathing cells and spinal cord repair. Keio J Med 54:8142005


Mackay-Sim AFéron FCochrane JBassingthwaighte LBayliss CDavies W: Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain 131:Pt 9237623862008


Maynard FM JrBracken MBCreasey GDitunno JF JrDonovan WHDucker TB: International standards for neurological and functional classification of cord injury. Spinal Cord 35:2662741997


Miedzybrodzki RTabakow PFortuna WCzapiga BJarmundowicz W: The olfactory bulb and olfactory mucosa obtained from human cadaver donors as a source of olfactory ensheathing cells. Glia 54:5575652006


Moreno-Flores MTAvila J: The quest to repair the damaged spinal cord. Recent Pat CNS Drug Discov 1:55632006


Mothe AJTator CH: Transplanted neural stem/progenitor cells generate myelinating oligodendrocytes and Schwann cells in spinal cord demyelination and dysmyelination. Exp Neurol 213:1761902008


Nomura HTator CHShoichet MS: Bioengineered strategies for spinal cord repair. J Neurotrauma 23:4965072006


Olson HERooney GEGross LNesbitt JJGalvin KEKnight A: Neural stem cell- and Schwann cell-loaded biodegradable polymer scaffolds support axonal regeneration in the transected spinal cord. Tissue Eng Part A 15:179718052009


Oudega M: Schwann cell and olfactory ensheathing cell implantation for repair of the contused spinal cord. Acta Physiol (Oxf) 189:1811892007


Oudega MMoon LDde Almeida Leme RJ: Schwann cells for spinal cord repair. Braz J Med Biol Res 38:8258352005


Oudega MXu XM: Schwann cell transplantation for repair of the adult spinal cord. J Neurotrauma 23:4534672006


Pearse DDPereira FCMarcillo AEBates MLBerrocal YAFilbin MT: cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nature Med 10:6106162004


Pearse DDSanchez ARPereira FCAndrade CMPuzis RPressman Y: Transplantation of Schwann cells and/or olfactory ensheathing glia into the contused spinal cord: survival, migration, axon association, and functional recovery. Glia 55:97610002007


Pereira JECosta LMCabrita AMCouto PAFilipe VMMagalhães LG: Methylprednisolone fails to improve functional and histological outcome following spinal cord injury in rats. Exp Neurol 220:71812009


Perry CMackay-Sim AFeron FMcGrath J: Olfactory neural cells: an untapped diagnostic and therapeutic resource. The 2000 Ogura Lecture. Laryngoscope 112:6036072002


Plant GWCurrier PFCuervo EPBates MLPressman YBunge MB: Purified adult ensheathing glia fail to myelinate axons under culture conditions that enable Schwann cells to form myelin. J Neurosci 22:608360912002


Rabinovich SSSeledtsov VIPoveschenko OVSenuykov VVTaraban VYYarochno VI: Transplantation treatment of spinal cord injury patients. Biomed Pharmacother 57:4284332003


Radtke CWewetzer K: Translating basic research into clinical practice or what else do we have to learn about olfactory ensheathing cells?. Neurosci Lett 456:1331362009


Raisman G: Olfactory ensheathing cells and repair of brain and spinal cord injuries. Cloning Stem Cells 6:3643682004


Raisman G: Repair of spinal cord injury by transplantation of olfactory ensheathing cells. C R Biol 330:6–75575602007


Ramón y Cajal S: Studies on the Degeneration and Regeneration of the Nervous System OxfordOxford University Press2 Vols1928


Rasouli ABhatia NSuryadevara SCahill KGupta R: Transplantation of preconditioned schwann cells in peripheral nerve grafts after contusion in the adult spinal cord. Improvement of recovery in a rat model. J Bone Joint Surg Am 88:240024102006


Reier PJ: Cellular transplantation strategies for spinal cord injury and translational neurobiology. NeuroRx 1:4244512004


Ribeiro-Resende VTPimentel-Coelho PMMesentier-Louro LAMendez RMMello-Silva JPCabral-da-Silva MC: Trophic activity derived from bone marrow mononuclear cells increases peripheral nerve regeneration by acting on both neuronal and glial cell populations. Neuroscience 159:5405492009


Richter MWRoskams AJ: Olfactory ensheathing cell transplantation following spinal cord injury: hype or hope?. Exp Neurol 209:3533672008


Ronsyn MWBerneman ZNVan Tendeloo VFIJorens PGPonsaerts P: Can cell therapy heal a spinal cord injury?. Spinal Cord 46:5325392008


Røsland GVSvendsen ATorsvik ASobala EMcCormack EImmervoll H: Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res 69:533153392009


Saberi HFiroozi MMoshayedi P: Preliminary results of Schwann cell transplantation for chronic spinal cord injuries. Neurosurgery 59:4622006. (Abstract)


Saberi HFiroozi MMoshayedi PAghayan HArjomand BHosseini K: Preliminary results of Schwann cell transplantation for chronic spinal cord injuries. Neurosurgery 62:14102008. (Abstract)


Saberi HMoshayedi PAghayan HRArjmand BHosseini SKEmami-Razavi SH: Treatment of chronic thoracic spinal cord injury patients with autologous Schwann cell transplantation: an interim report on safety considerations and possible outcomes. Neurosci Lett 443:46502008


Saito FNakatani TIwase MMaeda YHirakawa AMurao Y: Spinal cord injury treatment with intrathecal autologous bone marrow stromal cell transplantation: the first clinical trial case report. J Trauma 64:53592008


Sasaki MLi BLankford KLRadtke CKocsis JD: Remyelination of the injured spinal cord. Prog Brain Res 161:4194332007


Schaal SMKitay BMCho KSLo TP JrBarakat DJMarcillo AE: Schwann cell transplantation improves reticulospinal axon growth and forelimb strength after severe cervical spinal cord contusion. Cell Transplant 16:2072282007


Schwartz MLazarov-Spiegler ORapalino OAgranov IVelan GHadani M: Potential repair of rat spinal cord injuries using stimulated homologous macrophages. Neurosurgery 44:104110461999


Sharp JKeirstead HS: Stem cell-based cell replacement strategies for the central nervous system. Neurosci Lett 456:1071112009


Someya YKoda MDezawa MKadota THashimoto MKamada T: Reduction of cystic cavity, promotion of axonal regeneration and sparing, and functional recovery with transplanted bone marrow stromal cell-derived Schwann cells after contusion injury to the adult rat spinal cord. Laboratory investigation. J Neurosurg Spine 9:6006102008


Steeves JDLammertse DCurt AFawcett JWTuszynski MHDitunno JF: Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures. Spinal Cord 45:2062212007


Tabesh HAmoabediny GNik NSHeydari MYosefifard MSiadat SO: The role of biodegradable engineered scaffolds seeded with Schwann cells for spinal cord regeneration. Neurochemistry Int 54:73832008


Takami TOudega MBates MLWood PMKleitman NBunge MB: Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat thoracic spinal cord. J Neurosci 22:667066812002


Turnbull VJCulturing human Schwann cells. Picot J: Human Cell Culture Protocols Totowa NJHumana Press2005. 173182


Tuszynski MHSteeves JDFawcett JWLammertse DKalichman MRask C: Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP Panel: clinical trial inclusion/exclusion criteria and ethics. Spinal Cord 45:2222312007


Weidner NBlesch AGrill RJTuszynski MH: Nerve growth factor-hypersecreting Schwann cell grafts augment and guide spinal cord axonal growth and remyelinate central nervous system axons in a phenotypically appropriate manner that correlates with expression of L1. J Comp Neurol 413:4955061999


Xu XMGuénard VKleitman NAebischer PBunge MB: A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp Neurol 134:2612721995


Xu XMOnifer SM: Transplantation-mediated strategies to promote axonal regeneration following spinal cord injury. Respir Physiol Neurobiol 169:1711822009


Xu YLiu LLi YZhou CXiong FLiu Z: Myelinforming ability of Schwann cell-like cells induced from rat adipose-derived stem cells in vitro. Brain Res 1239:49552008


Yoon SHShim YSPark YHChung JKNam JHKim MO: Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial. Stem Cells 25:206620732007


Zeman RZBaumana WAWen XOuyang NEtlinger JDCardozoa CP: Improved functional recovery with oxandrolone after spinal cord injury in rats. Neuroreport 20:8648682009


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