义翘讲堂《类器官研究领域快速崛起的“基石”：细胞因子》

类器官研究领域快速崛起的“基石”：细胞因子李田子,Ph.D.

高级产品经理北京义翘神州科技股份有限公司05-2024义翘神州CONTENT类器官与细胞因子1类器官培养的关键细胞因子“配方”2经类器官培养验证的细胞因子3义翘神州类器官与细胞因子01义翘神州类器官研究-市场情况义翘神州In2023，TheglobalorganoidsandspheroidsmarketsizewasestimatedatUSD1.1billionCAGR(2024-2032):19.1%Source:ByEnd-UseBiotchenology&PharmaceuticalindustriesAcademic&ResearchinstitutesHospitals&DiagnosticCenters类器官研究-市场情况义翘神州√√√√√HanbyeolLee;etal./10.51335/organoid.2021.1.e11.Paper：NCBI-PubMedCentralClinicaltrials：Organoid-223studies类器官研究-研究进展Source:https://ClinicalTUntil05/06/2024RegionNameStudies#World223Europe95NorthAmerica50EastAsia53……Conditionsby

AlphabeticalStudies#DigestiveSystemDiseases90Carcinoma61EndocrineSystemDiseases35UrogenitalDiseases32BreastNeoplasms31……义翘神州类器官研究-潜在应用义翘神州Figure.PotentialapplicationsofhumanorganoidsBasicresearch-Cell-to-cellinteractionsMechanismsofstemcellhomeostasisBiobankingDiseasemodeling-Mechanismsofhumandiseases-InheritablegeneticdisordersDrug-screeninganalysesPrecisionmedicine-Responsetodrugs-ResourcesforregenerativemedicinecoupledwithgeneticengineeringJihoonKim;etal./10.1038/s41580-020-0259-3.类器官研究-疾病模型2024年4月24日,Nature刊发了一篇类关于脑器官相关的研究文章Timothy综合征：自闭症、神经系统问题的遗传性疾病，由CACNA1C基因突变引起。在小鼠模型中，相关突变并不总是能引起与人类疾病相同的症状。类器官解决这一难题。hiPS分化建立hCO，移植到搭上发育皮层，与其大脑整合。干细胞（hiPS）：从Timothy综合征的患者提取获得hCO：humancorticalorganoids义翘神州XiaoyuChen;etal./10.1038/s41586-024-07310-6

肠道类器官-疾病模型作者感染模型干细胞来源Ettayebietal.(2016)HIEsgeneratedfromstemcellsofhumanintestinalcryptsStemcellsisolatedfromintestinalcryptsinhumanintestinaltissuesZhangetal.(2017)HIOsdevelpedfromhumanPSCPSClineWA01(non-secretor)andWA09(secretor)Satoetal.(2017)IECsdevepedfromhumaniPSCHumaniPSCline三种研究诺如病毒感染的肠道类器官模型诺如病毒疫苗和治疗的研究缺少可耐受的小动物模型缺少可用于繁殖这种RNA病毒的的体外细胞培养系统等问题3D肠道类器官挑战义翘神州HIE:humanintestinalenteroid

IEC:IntestinalepithelialcellsHIO:humanintestinalorganoidJeHyoungKim;etal./10.4167/jbv.2068.肠道类器官-药物筛选应用场景疾病研究题目临床#药物筛选结直肠癌ProspectiveObservationontheAccuracyofinVitroScreeningofColorectalCancerChemotherapyDrugsBasedonOrganoids-ona-chipNCT04996355TheCultureofAdvanced/Recurrent/MetastaticColorectalCancerOrganoidsandDrugScreeningNCT05304741Patient-derivedOrganoidsofRAS/RAFWild-typeMetastaticRightColonCancertoTesttheSensitivityandClinicalConsistencyofCombinedTreatmentofCetuximab.NCT04906733AProspectiveMulticenterRandomizedControlledTrialoftheClinicalEfficacyofNeoadjuvantTherapyBasedonOrganoidsDrugSensitivityVersusEmpiricalNeoadjuvantTherapyintheTreatmentofAdvancedRectalCancerNCT05352165义翘神州QinyingWang;etal./10.1038/s41392-022-01194-6.脑类器官培养过程脑类器官的培养过程1.扩增诱导多能干细胞(iPSC)2.放入的基质胶(Matrigel)使干细胞发育成脑类器官3.培养基中通常加入所需的细胞因子义翘神州AnaBelénGarcía-Delgado;etal./10.3390/ani12223150.肠道类器官培养过程类器官培养过程：(A–C)Afterthestartofcryptculture,theupperopeningrapidlybecomesealed.(D–F)Then,thelumenisfilledwithapoptoticcells.(G,H)Thecryptregionundergoescontinuousbuddingevents.(D–H)Asterisksindicatethelumen.(G,H)Whitearrowsindicatecryptbudding.1.扩增小鼠小肠隐窝细胞，包埋在基质胶中2.培养基加入细胞因子：比如EGF、Noggin和RSPO1义翘神州ToshioTakahashi;etal./10.3390/ijms222010912.类器官培养的关键细胞因子“配方”02义翘神州BDNF、GDNF中脑类器官FGF2、InsulinVEGFEGF、Noggin脑类器官培养-主要细胞因子小脑类器官将多能细胞分化为神经外胚层谱系脑类器官生成血管引导细胞沿特定器官谱系分化分化和成熟义翘神州BenjaminGalet;etal./10.3389/fneur.2020.01005.PraveenJosephSusaimanickam;etal./10.15283/ijsc22006.

JayGopalakrishnan./10.1002/bies.201900011.GuiniSong;etal.

/10.3389/fncel.2021.646921.脑类器官-疾病模型不同类型脑类器官疾病模型/潜在应用大脑/早期大脑类器官遗传引起的小头畸形寨卡病毒引起的小头畸形米勒-迪克综合征*中脑类器官帕金森病潜在模型下丘脑类器官激素和代谢紊乱潜在模型腺垂体类器官垂体功能障碍的潜在模型海马类器官阿尔茨海默病引起的认知功能障碍的潜在模型小脑类器官脊髓小脑共济失调和丹迪-沃克综合征**的潜在模型背侧端脑类器官自闭症谱系障碍前脑组合体蒂莫西综合症***义翘神州JayGopalakrishnan./10.1002/bies.201900011.*米勒-迪克综合征:无脑回畸形为特征的病症***蒂莫西综合症:一种罕见的多系统遗传性疾病**丹迪-沃克综合征:小脑发育不正常脑类器官培养-主要细胞因子不同类型脑类器官培养所需试剂小脑类器官SB431542,FGF2,FGF19,SDF1背侧端脑类器官Noggin,FGF2,DKK1,EGF,ascorbicacid,BDNF,GDNF,cAMP小脑板神经上皮FGF2,4,8,SAG,retinoicacid,BDNF,GDNF,NT3中脑类器官SB-431542,Noggin,CHIR99021,SHH,FGF8,BDNF,

GDNFandacAMPpathwayactivator腺垂体类器官DAPT,SAG,BIO,BMP4,dorsomorphin,Wnt4,Wnt5,FGF8,Nodal,iWP2海马类器官WntinhibitorIWR1e,TGF-βinhibitorSB431542,10%FBS,GSK3inhibitorCHIR99021,BMP4前脑类器官Dorsomorphin(BMPinhibitor),A83(BMPandTGFβinhibitor),SB-431542,WNT3A,CHIR99021(GSK3βinhibitor),BDNFandGDNF义翘神州ElizabethDiLullo;etal./10.1038/nrn.2017.107.JayGopalakrishnan./10.1002/bies.201900011.RSPO-1EGFNogginWnt肠道类器官培养-主要细胞因子肠道类器官激活小肠隐窝的Wnt信号协助小肠增殖隐窝数量增多维持肠道干细胞义翘神州ToshiroSato;etal./10.1053/j.gastro.2011.07.050.肠道类器官-不同种属培养试剂差异种属器官干细胞培养条件BasalculturemediumEGFNogginRSPO-1Wnt3aNicotinamideGastrinA-83-01SB202190MouseSmallintestine√√√√Colon√√√√√HumanSmallintestine√+gastrin√√√√√√√√Colon√+gastrin√√√√√√√√义翘神州ToshiroSato;etal./10.1053/j.gastro.2011.07.050.Figure.Human-derivedorganoids类器官研究-相关细胞因子BrainBreastLungProstatePancreaticHeartIntestinalGastricLiverEGFEGFEGFEGFEGFEGFFGF2FGF2FGF2FGF2FGF2FGF2FGF2FGF7TGFB1FGF10FGF10FGF10FGF10FGF10FGF10FGF10NOGNOGNOGNOGNOGNOGNOGNOGINHBAINHBAINHBAINHBAHGFRSPO1RSPO1RSPO1RSPO1RSPO1RSPO1RSPO1OSMDKK1DKK1GDNFLIF义翘神州OVARYBRAINBREASTLUNGSKIDNEYBLADDERPROSTATEEYESINNEREARESOPHAGUSSTOMACHINTESTINEandCOLONLIVERPANCREASBenedettaArtegiani;etal./10.1093/hmg/ddy187.经类器官培养验证的细胞因子03义翘神州细胞因子产品线特点概述GMP认证书250+细胞因子类分子，800+细胞因子类产品按照ISO9001:2015和ISO13485:2016质量管理体系要求进行生产涉及免疫细胞培养、干细胞研究、类器官培养等热门应用领域覆盖生长因子、趋化因子、干扰素、白介素、淋巴因子等严格质控造就更优细胞活性高批间一致性高纯度（20+GMP级细胞因子）义翘神州2024年值得关注的生长因子供应商细胞因子产品设计种属多：Human、Mouse、Monkey等，尽可能满足不同的动物实验模型倾向于无标签或者小标签真核或者原核表达系统低内毒素活性有竞争力应用场景数据展示义翘神州细胞因子产品设计多种属：Human、Mouse、Monkey等，尽可能满足不同的动物实验模型的需求义翘神州用于小肠隐窝分离和类器官培养小鼠小肠隐窝富集包埋在Matrigel中接种到24孔板上添加类器官培养基每2天更换新鲜培养基AdvancedDMEM/F12medium50ng/mLMouseEGF(SinoBiological,50482-MNCH)100ng/mLMouseNoggin(SinoBiological,50688-M02H)500ng/mLHumanR-spondin1(SinoBiological,11083-HNAS)培养主要组成YuanchuangLi;etal./10.1016/j.stemcr.2020.12.005.细胞因子产品设计低内毒素LPS处理的胚状体中胚层的生物标志物会消失且不能分化成有功能的成骨细胞LPS处理的胚状体会出现凋亡的现象义翘神州KavithaSivasubramaniyan;etal./10.2217/1746073.细胞因子产品设计应用场景数据展示-1：类器官应用场景义翘神州产品详情页下拉点开产品详情页细胞因子产品设计应用场景数据展示-2：免疫细胞应用场景CD14+

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DCs义翘神州高纯度血管类器官培养FGF2/bFGF10014-HNAE类器官培养相关产品数据iPSC-derivedhumanvascularorganoids(Day7)wereculturedwithFGF2(10014-HNAE),VEGF165(11066-HNAH),EGF(10605-HNAE).Redarrowsrepresentvascularorganoids.Imagetakenat10xmagnification.VEGF16511066-HNAH高纯度≥95%义翘神州≥95%类器官培养相关产品数据KGF/FGF-750394-M07E小鼠膀胱类器官培养MouseBladderOrganoidsafter14daysinculture25ng/mLofRecombinantMouseKGF/FGF-7Protein(50394-M07E)

wasusedfor2weeksinBMEsubmergedinmousebladdermedia.DataprovidedbyDr.YinatWashingtonUniversity,St.Louis,MO.义翘神州国外知名品牌义翘批次1义翘批次2活性比较数据批间一致性数据MeasuredinacellproliferationassayusingBalb/C3T3mouseembryonicfibroblasts.EGF10605-HNAE义翘神州批次1义翘神州批次2义翘神州批次3国外知名品牌义翘神州批次1义翘神州批次2经过14天的培养肠道类器官肠道类器官培养-文献中产品应用案例1肠损失后的肠道再生义翘神州小鼠小肠隐窝富集包埋在Matrigel中接种到24孔板上添加类器官培养基每2天更换新鲜培养基AdvancedDMEM/F12medium50ng/mLMouseEGF(SinoBiological,50482-MNCH)100ng/mLMouseNoggin(SinoBiological,50688-M02H)500ng/mLHumanR-spondin1(SinoBiological,11083-HNAS)培养主要组成YuanchuangLi;etal./10.1016/j.stemcr.2020.12.005.结直肠癌类器官肠道类器官培养-文献中产品应用案例2义翘神州结直肠癌患者耐药性的研究AdvancedDMEM/F12medium50ng/mLMouseEGF(SinoBiological,50482-MNCH)100ng/mLMouseNoggin(SinoBiological,50688-M02H)500ng/mLHumanR-spondin1(SinoBiological,11083-HNAS)培养主要组成结直肠癌组织分离原代培养包埋在Matrigel中接种到24孔板上添加类器官培养基每3天更换新鲜培养基结直肠癌类器官用于：药敏试验转录组测序LifengChen;etal./10.3389/fonc.2022.855674.其他类器官培养-文献中产品应用案例滋养层类器官扩增潜力干细胞-滋养层干细胞来源的滋养层类器官义翘神州50ng/mLHumanHGF(SinoBiological,10463-HNAS)50ng/mLHumanEGF80ng/mLHumanR-spondin1(SinoBiological,11083-HNAS)培养中用到的细胞因子100ng/mLHumanFGF2DegongRuan;etal./10.1016/j.xcrm.2022.100849.类器官培养相关产品数据义翘神州活性比较数据批间一致性数据MeasuredbyitsabilitytoinduceactivationofßcateninresponseinaTopflashLuciferaseassayusingHEK293Thumanembryonickidneycells.RSPO111083-HNAS国外知名品牌义翘神州义翘神州批次1义翘神州批次2义翘神州批次3活性比较数据批间一致性数据MeasuredbyitsabilitytoneutralizeTGF-betamediatedinhibitiononMv-1-Lucellproliferation.HGF10463-HNAS义翘神州国外知名品牌义翘神州批次1义翘神州批次2义翘神州批次3不同时间点颅咽管瘤类器官的形态

脑肿瘤类器官脑类器官培养-文献中产品应用案例1义翘神州10ng/mLHumanFGF10(SinoBiological,10573-HNAE)10ng/mLHumanEGF(SinoBiological,10605-HNAE)培养中用到的细胞因子Xiao-YanTang;etal./10.1038/s41392-022-01024-9.类器官培养相关产品数据活性比较数据活性比较数据CellproliferationassayusingBaF3mousepro-BcellstransfectedwithhumanFGFR2b.CellproliferationassayusingBaF3mousepro-BcellstransfectedwithhumanFGFR2b.义翘神州FGF7/KGF10210-H07EFGF1010573-HNAE≥95%≥95%国外知名品牌义翘神州国外知名品牌义翘神州类器官培养相关产品数据

InhibitproliferationofMPC-11cells.>1000U/mgCellproliferationassayusingTF-1humanerythroleukemiccells.>30,000Units/μg≥95%≥95%活性比较数据批间一致性数据义翘神州义翘神州国外知名品牌义翘神州批次1义翘神州批次2

GMP级HumanActivinAGMP-10429-HNAH

GMP级HumanOSMGMP-10452-HNAH经不同类器官培养验证的细胞因子义翘神州人肠癌类器官人结直肠类器官HumanintestinalcancerorganoidswereculturedwithRSPO1(11083-HNAS),EGF(50482-MNCH),NOG(50688-M02H).(Routinelytested).DataprovidedbyD1MedicalTechnologyHumancolorectumorganoidswereculturedwithRSPO1(11083-HNAS),EGF(50482-MNCH),NOG(50688-M02H).(Routinelytested).DataprovidedbyD1MedicalTechnology.义翘神州人肺癌类器官人肺类器官HumanlungcancerorganoidswereculturedwithFGF2(10014-HNAE),FGF4(16043-HNAE),FGF7(10210-H07E),EGF(50482-MNCH),FGF10(10573-HNAE),NOG(50688-M02H),RSPO1(11083-HNAS).(Routinelytested).DataprovidedbyD1MedicalTechnology.HumanlungorganoidswereculturedwithFGF2(10014-HNAE),FGF4(16043-HNAE),FGF7(10210-H07E),EGF(50482-MNCH),FGF10(10573-HNAE),NOG(50688-M02H),RSPO1(11083-HNAS).(Routinelytested).DataprovidedbyD1MedicalTechnology.经不同类器官培养验证的细胞因子义翘神州人肝癌类器官人胆管癌类器官HumanlivercancerorganoidswereculturedwithFGF2(10014-HNAE),HGF(10463-HNAS),FGF7(10210-H07E),EGF(50482-MNCH),FGF10(10573-HNAE),TGFB1(10804-HNAC),NOG(50688-M02H),RSPO1(11083-HNAS).(Routinelytested).DataprovidedbyD1MedicalTechnology.HumancholangiocarcinomasorganoidswereculturedwithFGF2(10014-HNAE),HGF(10463-HNAS),FGF7(10210-H07E),EGF(50482-MNCH),FGF10(10573-HNAE),NOG(50688-M02H),RSPO1(11083-HNAS).(Routinelytested).DataprovidedbyD1MedicalTechnology.经不同类器官培养验证的细胞因子义翘神州人肾癌类器官人肾类器官HumankidneycancerorganoidswereculturedwithFGF2(10014-HNAE),FGF7(10210-H07E),EGF(50482-MNCH),FGF10(10573-HNAE),NOG(50688-M02H),RSPO1(11083-HNAS).(Routinelytested).DataprovidedbyD1MedicalTechnology.HumankidneyorganoidswereculturedwithFGF7(10210-H07E),EGF(50482-MNCH),FGF10(10573-HNAE),NOG(50688-M02H),RSPO1(11083-HNAS),HGF(10463-HNAS),FGF4(16043-HNAE).(Routinelytested).DataprovidedbyD1MedicalTechnology.经不同类器官培养验证的细胞因子义翘神州人胃癌类器官人胃类器官HumangastriccancerorganoidswereculturedwithEGF(50482-MNCH),

FGF10(10573-HNAE),NOG(50688-M02H),RSPO1(11083-HNAS).(Routinelytested).DataprovidedbyD1MedicalTechnologyHumanstomachorganoidsorganoidswereculturedwithEGF(50482-MNCH),FGF10(10573-HNAE),NOG(50688-M02H),RSPO1(11083-HNAS).(Routinelytested).DataprovidedbyD1MedicalTechn