神经系统疾病研究的新兴工具：脑类器官

神经系统疾病研究的新兴工具：脑类器官前言大脑复杂的细胞组成和特定的结构，使得体外建模难度极大。近年来大脑类器官概括了大脑发育的许多关键特征，激发全球神经学领域相关科研人员的兴趣，研究成果不断的发表于高分期刊，将脑类器官用于各种生理和病理研究。细胞因子作为类器官培养基中的添加试剂，可以引导细胞按特定器官谱系进行分化。为助力脑类器官的培养与分化，义翘神州可提供人EGF、FGF2、NOG、BMP4等一系列脑类器官培养相关产品。01脑类器官研究新进展目前大多数脑部模型主要是人类死后脑组织、非人灵长类动物组织或者体外2D细胞。由于资源限制和动物模型的物种差异性等原因，使脑类器官成为潜在研究脑部生理和病理的模型。脑类器官主要源自胚胎干细胞（ESC）或者诱导性多能干细胞（iPSC）。对于体外神经生物学和神经发育障碍的疾病的研究，也会用到不同部位的脑类器官，比如前脑、中脑、海马脑类器官等。目前使用脑类器官模型涉及到阿尔茨海默症、帕金森病、自闭症、精神分裂等，甚至包括渐冻症、结节性硬化症等罕见病。体外神经生物学和神经发育障碍疾病模型的脑类器官TypeoforganoidDiseasemodeled/potentialapplicationCerebral/earlybrainorganoidsGeneticallycausedmicrocephalyZikavirusmediatedmicrocephalyMiller–DiekersyndromeMidbrainorganoidsPotentialtomodelParkinson'sdiseaseHypothalamusorganoidsPotentialtomodelhormonalandmetabolicdisordersincludingPrader–WillisyndromeAdenohypophysisorganoidsPotentialtomodelpituitarydysfunctionHippocampusorganoidsPotentialtomodelcognitivedysfunctionsduetoAlzheimer'sdiseaseCerebellumorganoidsPotentialtomodelSCAandDandy–WalkersyndromeDorsaltelencephalonorganoidsASDForebrainassembloidsTimothysyndromeASD,autismspectrumdisorders;POMC,pro-opiomelanocortin.（源自：/10.1002/bies.201900011）02细胞因子在脑类器官中的应用细胞因子在类器官培养过程中发挥重要作用。在多能干细胞（PSC）培养中加入了FGF2构建3D脑类器官模型。对于不同部位的脑类器官的培养，会加入不同的细胞因子，比如对于用于研究脊髓小脑共济失调疾病的小脑类器官培养中，会加入FGF2、FGF19、SDF1等细胞因子。用于生成特异性脑类器官的因子摘要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）✦义翘神州细胞因子产品数据HumanFGF2Protein,Cat:GMP-10014-HNAE高纯度：≥95%asdeterminedbySDS.结合活性CellproliferationassayusingBalb/C3T3mouseembryonicfibroblasts.Thespecificactivityis>1,000IU/μg.HumanNogginProtein,Cat:10267-HNAH高纯度：≥95%asdeterminedbySDS.≥95%asdeterminedbySEC-HPLC.高批间一致性InhibitBMP4-inducedalkalinephosphataseproductionbyMC3T3E1mousepreosteoblastcells.脑类器官培养相关的细胞因子货号靶点内毒素纯度及活性\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【参考文献】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