神經(jīng)系統(tǒng)疾病研究的新興工具：腦類器官

神經(jīng)系統(tǒng)疾病研究的新興工具：腦類器官前言大腦復(fù)雜的細(xì)胞組成和特定的結(jié)構(gòu)，使得體外建模難度極大。近年來大腦類器官概括了大腦發(fā)育的許多關(guān)鍵特征，激發(fā)全球神經(jīng)學(xué)領(lǐng)域相關(guān)科研人員的興趣，研究成果不斷的發(fā)表于高分期刊，將腦類器官用于各種生理和病理研究。細(xì)胞因子作為類器官培養(yǎng)基中的添加試劑，可以引導(dǎo)細(xì)胞按特定器官譜系進行分化。為助力腦類器官的培養(yǎng)與分化，義翹神州可提供人EGF、FGF2、NOG、BMP4等一系列腦類器官培養(yǎng)相關(guān)產(chǎn)品。01腦類器官研究新進展目前大多數(shù)腦部模型主要是人類死后腦組織、非人靈長類動物組織或者體外2D細(xì)胞。由于資源限制和動物模型的物種差異性等原因，使腦類器官成為潛在研究腦部生理和病理的模型。腦類器官主要源自胚胎干細(xì)胞（ESC）或者誘導(dǎo)性多能干細(xì)胞（iPSC）。對于體外神經(jīng)生物學(xué)和神經(jīng)發(fā)育障礙的疾病的研究，也會用到不同部位的腦類器官，比如前腦、中腦、海馬腦類器官等。目前使用腦類器官模型涉及到阿爾茨海默癥、帕金森病、自閉癥、精神分裂等，甚至包括漸凍癥、結(jié)節(jié)性硬化癥等罕見病。體外神經(jīng)生物學(xué)和神經(jīng)發(fā)育障礙疾病模型的腦類器官TypeoforganoidDiseasemodeled/potentialapplicationCerebral/earlybrainorganoidsGeneticallycausedmicrocephalyZikavirusmediatedmicrocephalyMiller–DiekersyndromeMidbrainorganoidsPotentialtomodelParkinson'sdiseaseHypothalamusorganoidsPotentialtomodelhormonalandmetabolicdisordersincludingPrader–WillisyndromeAdenohypophysisorganoidsPotentialtomodelpituitarydysfunctionHippocampusorganoidsPotentialtomodelcognitivedysfunctionsduetoAlzheimer'sdiseaseCerebellumorganoidsPotentialtomodelSCAandDandy–WalkersyndromeDorsaltelencephalonorganoidsASDForebrainassembloidsTimothysyndromeASD,autismspectrumdisorders;POMC,pro-opiomelanocortin.（源自：/10.1002/bies.201900011）02細(xì)胞因子在腦類器官中的應(yīng)用細(xì)胞因子在類器官培養(yǎng)過程中發(fā)揮重要作用。在多能干細(xì)胞（PSC）培養(yǎng)中加入了FGF2構(gòu)建3D腦類器官模型。對于不同部位的腦類器官的培養(yǎng)，會加入不同的細(xì)胞因子，比如對于用于研究脊髓小腦共濟失調(diào)疾病的小腦類器官培養(yǎng)中，會加入FGF2、FGF19、SDF1等細(xì)胞因子。用于生成特異性腦類器官的因子摘要TypeoforganoidCulturedwithMidbrainorganoidsWnt

activatorsandSMADinhibitorsHypothalamusorganoidsInhibitorsthatblocks

TGF‐βpathwaysBMP-4

ligandandWntagonistsAdenohypophysisorganoidsDAPT,SAG,BIO,BMP4,dorsomorphin,

Wnt4,

Wnt5,

FGF8,

Nodal,iWP2HippocampusorganoidsWntinhibitorIWR1e,TGF‐βinhibitorSB431542,10%FBS,GSK3inhibitorCHIR99021,BMP4CerebellumorganoidsSB431542,

FGF2,

FGF19,

SDF1DorsaltelencephalonorganoidsNoggin,FGF2,rhDKK1,

EGF,ascorbicacid,

BDNF,

GDNF,cAMPDorsaltelencephalonorganoidsDorsomorphin,SB431542,FGF2,EGFSubpallium:IWP2,SHHagonistSAG,BDNF,NT3,allopregnalone,retinoicacidPallium:BDNF,NT3Photosensitiveorganoids\o"/recombinant-proteins/mouse-bdnf-50240-m08h"BDNFRetinalorganoidsIWR1e,Matrigel,10%FBS,SAG,CHIR99021,retinoicacidHypothalamusorganoidsSMAD,BMP,NodalandactivinsignalingpathwayinhibitorsCerebellarplateneuroepitheliumFGF2,4,8,SAG,retinoicacid,BDNF,GDNF,NT3BDNF,brain‐derivedneurotrophicfactor;BMP,bonemorphogeneticprotein;cAMP,cyclicadenosinemonophosphate;EGF,epidermalgrowthfactor;FBS,fetalbovineserum;FGF,fibroblastgrowthfactor;GDNF,glialcell‐derivedneurotrophicfactor.（源自：/10.1002/bies.201900011）?義翹神州細(xì)胞因子產(chǎn)品數(shù)據(jù)HumanFGF2Protein,Cat:GMP-10014-HNAE高純度：≥95%asdeterminedbySDS.結(jié)合活性CellproliferationassayusingBalb/C3T3mouseembryonicfibroblasts.Thespecificactivityis>1,000IU/μg.HumanNogginProtein,Cat:10267-HNAH高純度：≥95%asdeterminedbySDS.≥95%asdeterminedbySEC-HPLC.高批間一致性InhibitBMP4-inducedalkalinephosphataseproductionbyMC3T3E1mousepreosteoblastcells.腦類器官培養(yǎng)相關(guān)的細(xì)胞因子貨號靶點內(nèi)毒素純度及活性\o"/recombinant-proteins/human-egf-10605-hnae"10605-HNAEEGF<5EU/mg≥95%☆，Active\o"/recombinant-proteins/human-egf-gmp-10605-hnae"GMP-10605-HNAEEGF<5EU/mg≥95%☆，Active\o"/recombinant-proteins/human-fgf2-gmp-10014-hnae"GMP-10014-HNAEFGF2<10EU/mg≥95%，Active\o"/recombinant-proteins/human-bmp4-10609-hnae2"10609-HNAE2BMP4<1EU/mg≥95%，Active\o"/recombinant-proteins/human-noggin-nog-10267-hnah"10267-HNAHNOG<10EU/mg≥95%☆，Active☆：SDS&SEC-HPLC【參考文獻】1.AntoineVergeretal.FDAApprovalofLecanemab:TheRealStartofWidespreadAmyloidPETUse?—TheEANMNeuroimagingCommitteePerspective.EuropeanJournalofNuclearMedicineandMolecularImaging,2023./10.1007/s00259-023-06177-5.2.YujungChangetal.ModellingNeurodegenerativeDiseaseswith3DBrainOrganoids.BiologicalReviews,2020./10.1111/brv.12626.3.JihoonKim,Bon-KyoungKoo,andJuergenA.Knoblich,HumanOrganoids:ModelSystemsforHumanBiologyandMedicine,NatureReviewsMolecularCellBiology,2020./10.1038/s41580-020-0259-3.4.GuiniSongetal.TheApplicationofBrainOrganoidTechnologyinStrokeResearch:ChallengesandProspects.FrontiersinCellularNeuroscience,2021./articles/10.3389/fncel.2021.646921.5.JayGopalakrishnan.TheEmergenceofStemCell-BasedBrainOrganoids:TrendsandChallenges.BioEssays,2019./10.1002/bies.201900011.6.MadelineA.LancasterandJuergenA.Knoblich.GenerationofCerebralOrganoidsfromHumanPluripotentStemCells.NatureProtocols,2014./10.1038/nprot.2014.158.7.Sebastian,R.,etal.Schizophrenia-associatedNRXN1deletionsinducedevelopmental-timing-andcell-type-specificvulnerabilitiesinhumanbrainorganoids.NatCommun,2023./10.1038/s41467-023-39420-68.JimenaAndersen,etal.GenerationofFunctionalHuman3DCortico-MotorAssembloids.Cell,2020,doi:10.1016/j.cell.2020.11.017.9.YueqiWang,etal.Modelinghumantelencephalicdevelopmentandautism-associatedSHANK3deficiencyusingorganoidsgeneratedfromsingleneuralrosettes.NatureCommunications,2022./10.1038/s41467-022-33364-z10.Fleck,J.S.,etal.Inferringand