Cell Therapy Against Cerebral Stroke: Comprehensive Reviews for Translational Researches and Clinical Trials PDF
Preview Cell Therapy Against Cerebral Stroke: Comprehensive Reviews for Translational Researches and Clinical Trials
Cell Therapy Against Cerebral Stroke Comprehensive Reviews for Translational Researches and Clinical Trials Kiyohiro Houkin Koji Abe Satoshi Kuroda Editors 123 Cell Therapy Against Cerebral Stroke Kiyohiro Houkin (cid:129) Koji Abe (cid:129) Satoshi Kuroda Editors Cell Therapy Against Cerebral Stroke Comprehensive Reviews for Translational Researches and Clinical Trials Editors KiyohiroHoukin KojiAbe DepartmentofNeurosurgery DepartmentofNeurology HokkaidoUniversityGraduate OkayamaUniversityGraduate SchoolofMedicine SchoolofMedicine Sapporo,Japan Okayama,Japan SatoshiKuroda GraduateSchoolofMedicineandPharmace DepartmentofNeurosurgery Toyama,Japan ISBN978-4-431-56057-9 ISBN978-4-431-56059-3 (eBook) DOI10.1007/978-4-431-56059-3 LibraryofCongressControlNumber:2016963678 ©SpringerJapanKK2017 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilarmethodologynowknownorhereafterdeveloped. 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East, 3-8-1 Nishi-Kanda, Chiyoda-ku, Tokyo101-0065,Japan Preface Discouragement and Hope MyseniorcolleaguesandIhaveopenedthedoortopreventingandminimizingthe occurrence of stroke by developing drugs such as antiplatelet agents, antihypertension medications, and many other drugs that suppress the risk factors ofstroke.Consequently,wehavesuccessfullyreducedtheoccurrenceofstroke.It maysoundsomewhatpessimistic,butIbelievethatthereductionoftheoccurrence of stroke by these drugs has reached a plateau. In other words, stroke is still a leadingcauseofdeathanddisabilityandwillcontinuetobe. Quite unfortunately, in spite of intensivebasicand clinical research, few treat- mentoptionsexistoncestrokeoccurs.Thatis,wecannotalwaysfavorablychange theclinicalcourseofpatientswithstroke.Onlyonepivotalchangeofstrategyhas taken place recently, which is the use of t-PA and mechanical thrombectomy (MT) with endovascular techniques. However, as is well known, the number of patientswhoarefortunateenoughtoreceivet-PAandMTislimited. Many promising drugs have demonstrated superb effectiveness in vitro and in vivo in reducing the damage due to stroke. However, most clinical trials unfortunately have proved to be failures. As a clinical neurosurgeon, I have been personally involved in many of these clinical trials. As can be imagined, I was overwhelmed by despair with the poor outcome of the trials. However, I am not alwaysdriventodespairintheinnovationofstroketreatmentusingdrugs. Possibility of a Bright Future of Cell Therapy It goes without saying for readers of this book who have a basic interest and knowledgeofcelltherapythatinthelate1990scellbiologydevelopedandbecame a ray of hope in the treatment of intractable disease. Because the injured neural v vi Preface tissue in the central nervous system (CNS) has limited regenerative capacity, the therapeutic potential of cell transplantation has been anticipated in various patho- logicalCNSconditions–forexample,traumaticspinalcordinjury,traumaticbrain injury, degenerative disease, demyelinating disease, and ischemic stroke. Espe- cially,thegrowingaccumulationofinformationandinducedevidencesuggestthat cell therapy holds great potential as stroke therapy. In this book, the authors describe recent advances and perspectives in cell therapy against stroke. First, they report on the specific issues regarding various cell sources including bone marrow-derived mononuclear cells(BMMNCs;Suda),bonemarrow stromalcells (BMSCs; Kuroda), neural stem cells/neuronal progenitor cells (NSCs/NPCs; Horie), and induced pluripotent stem cells/induced neuronal cells (iPSCs/iNCs; Abeetal.).Second,theyreportonspecificissueshavingtodowiththeprotocolin pre-clinical developments and early-stage clinical trials including cell culture (Ito etal.), celldelivery(Kawabori),scaffolding incell therapy (Osanai),bio-imaging forcelltracking(Sugiyamaetal.),andfunctionalbio-imaging(Saito).Third,they review the previous clinical trials and the development of guidelines for cell therapy(Shichinohe),andtheirongoingclinicaltrials(KasaharaandHonmou). Pleasure in Overcoming the Hurdles Ascanbeimagined,onceweopennewdoors,anotherhurdleappears.Forexample, such effects as dose-dependence in conventional pharmacokinetics cannot always be evaluated in the effects of cell therapy. We have to develop novel methods of evaluation of cell therapy. The many ethical problems to be resolved can also be imagined.Inaddition,thehealthcostissuesassociatedwithregenerativemedicine is likely to be focused on in the future. Thus, the indication of the treatment is closelyrelatedtothebalancebetweenthecostandtheimprovementofthequality of life (QOL) from regenerative medicine. Because stroke often causes serious sequelae such as hemiparesis, aphasia, and dementia, direct medical expenses, nursing-care costs, and the social loss by deterioration of QOL of not only the patientbutalsothefamilycanarisefromthosesequelae.Ontheotherhand,large expensesarealsoanticipatedforcelltherapyagainststrokebecauseitisacommon disease.Wemustconsiderthecost-effectivenessandtheappropriatedistributionof healthresourcesbasedonourpresenthealthcaresystem,otherwiseithasnofuture. Moreover,asIhavementioned,itiswellknownthatregenerativemedicinehas variousintrinsicbioethicalissues,suchastheneedtodestroyafertilizedeggwhen making an embryonicstemcell, cell transplantationfor Parkinson’s disease using cells derived from an aborted fetus, and the possibility of human cloning. More- over, there are specific issues inthe field ofcell therapy for CNSdisorders. Since theearly2000s,neuroethicalissueshavearisenalongwiththedevelopmentofthe neurosciencessuchasneuromodulationbydeepbrainstimulation(DBS)orbrain– machine interface (BMI). In the future, cell therapy will be a major target of Preface vii neuroethical considerations – for example, issues regarding enhancement due to cell transplantation or the issues of chimerism with allogeneic or xenogeneic cell transplantsintheCNS.Wemustpayseriousattentiontoresearchethicsbecauseof thespecificityofourresearchfield. Ihopethatthisbookwillcontributetothedevelopmentofcelltherapyandoffer aplatformforfurtherdiscussionofcelltherapy.Aboveall,weauthorswillbevery happyifthisbookinvokestheinterestofmanyresearchersandcliniciansincluding those who have not committed to these fields to date. We are confident that cell therapywilldevelopasanindispensableoptionforthetreatmentofstrokeandother intractablediseases. DepartmentofNeurosurgery KiyohiroHoukin HokkaidoUniversityGraduate SchoolofMedicine Sapporo,Japan ClinicalResearchand HideoShichinohe MedicalInnovationCenter HokkaidoUniversityHospital Sapporo,Japan Contents PartI OptimalCellCources 1 BoneMarrow-DerivedMononuclearCells. . . . . . . . . . . . . . . . . . . 3 SatoshiSuda 2 CellTherapyforIschemicStrokewithBoneMarrow StromalCells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 SatoshiKuroda,HideoShichinohe,andKiyohiroHoukin 3 NeuralStemCells/NeuronalProgenitorCells. . . . . . . . . . . . . . . . . 27 NobutakaHorie 4 iPSCellsandiNCells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 ToruYamashitaandKojiAbe PartII TranslationalResearches 5 CellCulture. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 MasakiItoandKiyohiroHoukin 6 Route,CellDose,andTiming. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 MasahitoKawabori 7 RoleofBiomaterialsasScaffoldinginCellTherapyforStroke. . . 87 ToshiyaOsanai 8 InVivoCellTrackingTechniquesforApplicationsinCentral NervousSystemDisorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 TakuSugiyama,SatoshiKuroda,andKiyohiroHoukin 9 FunctionalBio-imaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 HisayasuSaito,MichiyukiMiyamoto,HideoShichinohe, KiyohiroHoukin,andSatoshiKuroda ix x Contents PartIII ClinicalTrials 10 ReviewofPreviousClinicalTrialsandGuidelines ofCellTherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 HideoShichinohe 11 IntravenousAutologousBoneMarrowMononuclearCell TransplantationforStrokePatients. . . . . . . . . . . . . . . . . . . . . . . . 135 YukikoKasahara,TomohiroMatsuyama,andAkihikoTaguchi 12 MesenchymalStemCells.. . . . .. . . . .. . . . .. . . . .. . . . .. . . . . .. 147 MasanoriSasakiandOsamuHonmou Part I Optimal Cell Cources
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