義翹講堂《類器官研究相關細胞因子的選擇》

類器官研究相關細胞因子的選擇北京義翹神州科技股份有限公司義翹神州CONTENT類器官研究進展1腸道和腦類器官介紹2細胞因子產(chǎn)品特色以及應用案例3義翹神州類器官研究進展01義翹神州類器官研究-市場情況(“OrganoidsandSpheroidsMarketSize|GlobalIndustryReport,2028”n.d.)(“OrganoidsMarketSize&ShareAnalysis-IndustryResearchReport-GrowthTrends”n.d.)CAGR(2021-2028)22.8%ByApplicationByEnd-UseByRegionDevelopmentalBiologyBiotchenology&PharmaceuticalindustriesLargestMarket:NorthAmericaPersonalizedMedicineAcademic&ResearchinstitutesFastestGrowingMarket:Asia-PacificRegenerativeMedicineHospitals&DiagnosticCentersDiseasePathplogyStudiesDrugToxicity&EfficacyTestingOrganoidsandspheroidsMarketAnalysis義翹神州類器官研究-研究進展Source:https://ClinicalTUntil09/05/2023RegionNameStudies#World180Europe74NorthAmerica42EastAsia41……義翹神州NCBI-PubMedCentral類器官研究發(fā)表文獻Clinicaltrials：Organoid-180studiesNCBI-PubMedCentral類器官研究發(fā)表文獻Clinicaltrials：Organoid-180studies類器官研究-研究進展RegionNameStudies#World180Europe74NorthAmerica42EastAsia41……Source:https://ClinicalTUntil09/05/2023Conditionsby

AlphabeticalStudies#DigestiveSystemDiseases77EndocrineSystemDiseases30BreastNeoplasms24SkinDiseases19LungDiseases17……義翹神州(Kim,Koo,andKnoblich2020)類器官研究-潛在應用LeftFigure.Potentialapplicationsofhumanorganoids.Basicresearch:-Cell-to-cellinteractionsMechanismsofstemcellhomeostasisBiobanking:Diseasemodeling:-Mechanismsofhumandiseases-InheritablegeneticdisordersDrug-screeninganalysesPrecisionmedicine:-Responsetodrugs-Resourcesforregenerativemedicinecoupledwithgeneticengineering義翹神州(ArtegianiandClevers2018)LeftFigure.Applicationsofhuman-derivedorganoids類器官研究-相關細胞因子BrainBreastLungProstatePancreaticHeartIntestinalGastricLiverEGFEGFEGFEGFEGFEGFFGF2FGF2FGF2FGF2FGF2FGF2FGF2FGF7TGFB1FGF10FGF10FGF10FGF10FGF10FGF10FGF10NOGNOGNOGNOGNOGNOGNOGNOGINHBAINHBAINHBAINHBAHGFRSPO1RSPO1RSPO1RSPO1RSPO1RSPO1RSPO1OSMDKK1DKK1GDNFLIF義翹神州OVARYBRAINBREASTLUNGSKIDNEYBLADDERPROSTATEEYESINNEREARESOPHAGUSSTOMACHINTESTINEandCOLONLIVERPANCREAS腸道和腦類器官介紹02義翹神州腸道類器官定義(Taelman,Diaz,andGuiu2022)人類腸道病生理研究有限的資源；動物種屬間差異等問題3D腸道類器官PSCISC挑戰(zhàn)義翹神州腸道類器官-研究領域(Takahashi,Fujishima,andKengaku2021),(Rubertetal.2020),(Güntheretal.2022)義翹神州腸道類器官培養(yǎng)-病毒感染研究作者感染模型干細胞來源Ettayebietal.(2016)HIEsgeneratedfromstemcellsofhumanintestinalcryptsStemcellsisolatedfromintestinalcryptsinhumanintestinaltissuesZhangetal.(2017)HIOsdevelpedfromhumanPSCPSClineWA01(non-secretor)andWA09(secretor)Satoetal.(2017)IECsdevepedfromhumaniPSCHumaniPSClineHIE:humanintestinalenteroid;HIO:humanintestinalorganoid.

IEC:intestinalepithelialcells(KimandJeong2020)三種研究諾如病毒感染的腸道類器官模型諾如病毒疫苗和治療的研究缺少可耐受的小動物模型缺少可用于繁殖這種RNA病毒的的體外細胞培養(yǎng)系統(tǒng)等問題3D腸道類器官挑戰(zhàn)義翹神州腸道類器官-研究領域(Takahashi,Fujishima,andKengaku2021),(Rubertetal.2020),(Güntheretal.2022)義翹神州腸道類器官-臨床研究(Wangetal.2022)應用場景疾病研究題目臨床#藥物篩選結(jié)直腸癌ProspectiveObservationontheAccuracyofinVitroScreeningofColorectalCancerChemotherapyDrugsBasedonOrganoids-ona-chipNCT04996355Patient-derivedOrganoidsofRAS/RAFWild-typeMetastaticRightColonCancertoTesttheSensitivityandClinicalConsistencyofCombinedTreatmentofCetuximab.NCT04906733AProspectiveMulticenterRandomizedControlledTrialoftheClinicalEfficacyofNeoadjuvantTherapyBasedonOrganoidsDrugSensitivityVersusEmpiricalNeoadjuvantTherapyintheTreatmentofAdvancedRectalCancerNCT05352165TheCultureofAdvanced/Recurrent/MetastaticColorectalCancerOrganoidsandDrugScreeningNCT05304741PilotStudyforExVivoTailoringofTreatmentinColorectalCancerNCT05401318義翹神州RSPO-1EGFNogginWnt腸道類器官培養(yǎng)-主要細胞因子(Satoetal.2011)腸道類器官激活小腸隱窩的Wnt信號協(xié)助小腸增殖隱窩數(shù)量增多維持腸道干細胞義翹神州腸道類器官培養(yǎng)過程(Takahashi,Fujishima,andKengaku2021)類器官培養(yǎng)過程：(A–C)Afterthestartofcryptculture,theupperopeningrapidlybecomesealed.(D–F)Then,thelumenisfilledwithapoptoticcells.(G,H)Thecryptregionundergoescontinuousbuddingevents.(D–H)Asterisksindicatethelumen.(G,H)Whitearrowsindicatecryptbudding.1.擴增小鼠小腸隱窩細胞，包埋在基質(zhì)膠中2.培養(yǎng)基加入細胞因子：比如EGF、Noggin和RSPO1義翹神州腸道類器官-不同種屬培養(yǎng)試劑差異種屬器官干細胞培養(yǎng)條件BasalculturemediumEGFNogginRSPO-1Wnt3aNicotinamideGastrinA-83-01SB202190MouseSmallintestine√√√√Colon√√√√√HumanSmallintestine√+gastrin√√√√√√√√Colon√+gastrin√√√√√√√√(Satoetal.2011)義翹神州腦類器官定義iPSCESC3D腦類器官具有與人類大腦類似結(jié)構和功能分區(qū)包含多種細胞類型，例如神經(jīng)祖細胞、神經(jīng)元、星形膠質(zhì)細胞和少突膠質(zhì)細胞形成過程模擬了胚胎發(fā)育過程中大腦的生長和發(fā)育過程(Agboolaetal.2021,Du2021,Clevers2016,Albaneseetal.2020)大腦功能研究神經(jīng)疾病研究等藥物篩選Figure:35dayscerebralorganoid義翹神州腦類器官培養(yǎng)過程(García-Delgadoetal.2022)腦類器官的培養(yǎng)過程1.擴增誘導多能干細胞（iPSC）2.放入的基質(zhì)膠（Matrigel），使干細胞發(fā)育成腦類器官3.培養(yǎng)基中通常加入所需的細胞因子義翹神州BDNF、GDNF中腦類器官FGF2、InsulinVEGFEGF、Noggin腦類器官培養(yǎng)-主要細胞因子(Galet,Cheval,andRavassard2020;Susaimanickam,Kiral,andPark2022;Gopalakrishnan2019;Songetal.2021)小腦類器官將多能細胞分化為神經(jīng)外胚層譜系腦類器官生成血管引導細胞沿特定器官譜系分化分化和成熟義翹神州腦類器官-疾病模型(Gopalakrishnan2019)不同類型腦類器官疾病模型/潛在應用大腦/早期大腦類器官-遺傳引起的小頭畸形-寨卡病毒引起的小頭畸形-米勒-迪克綜合征*中腦類器官-帕金森病潛在模型下丘腦類器官-激素和代謝紊亂潛在模型腺垂體類器官-垂體功能障礙的潛在模型海馬類器官-阿爾茨海默病引起的認知功能障礙的潛在模型小腦類器官-脊髓小腦共濟失調(diào)和丹迪-沃克綜合征**的潛在模型背側(cè)端腦類器官-自閉癥譜系障礙前腦組合體-蒂莫西綜合癥****米勒-迪克綜合征:無腦回畸形為特征的病癥；**丹迪-沃克綜合征:小腦發(fā)育不正常；***蒂莫西綜合癥:一種罕見的多系統(tǒng)遺傳性疾病義翹神州腦類器官培養(yǎng)-主要細胞因子(DiLulloandKriegstein2017;Gopalakrishnan2019)不同類型腦類器官培養(yǎng)所需試劑小腦類器官-SB431542,FGF2,FGF19,SDF1背側(cè)端腦類器官-Noggin,FGF2,DKK1,EGF,ascorbicacid,BDNF,GDNF,cAMP小腦板神經(jīng)上皮-FGF2,4,8,SAG,retinoicacid,BDNF,GDNF,NT3中腦類器官-SB-431542,Noggin,CHIR99021,SHH,FGF8,BDNF,GDNFandacAMPpathwayactivator腺垂體類器官-DAPT,SAG,BIO,BMP4,dorsomorphin,Wnt4,Wnt5,FGF8,Nodal,iWP2海馬類器官-WntinhibitorIWR1e,TGF-βinhibitorSB431542,10%FBS,GSK3inhibitorCHIR99021,BMP4前腦類器官-Dorsomorphin(BMPinhibitor),A83(BMPandTGFβinhibitor),SB-431542,WNT3A,CHIR99021(GSK3βinhibitor),BDNFandGDNF義翹神州腦類器官-新型模型神經(jīng)相關疾病治療難點：治療藥物穿過BBB到達CNS的靶向區(qū)域BBB:血腦屏障CNS:中樞神經(jīng)系統(tǒng)BECs:腦內(nèi)皮細胞改善藥物傳遞效率的方法：生成模擬配體的血管肽，與低密度脂蛋白受體相關蛋白1(LRP1)結(jié)合用細胞穿透肽來標記藥物分子動物原代BECs活檢獲得的人原代BECs血腦屏障類器官BBB體外模型(QianandTCW2021)iPSCFigureA：血腦屏障類器官的培養(yǎng)過程義翹神州腦類器官-新型模型腦類器官局限：缺乏中樞神經(jīng)系統(tǒng)脈管系統(tǒng)等血管化腦類器官(QianandTCW2021)FigureB-D：不同血管化類器官的培養(yǎng)過程生物材料輔助制造自發(fā)血管化限制灌注引起細胞壞死阻礙皮質(zhì)板形成和大腦結(jié)構成熟誘導最外層神經(jīng)過早分化義翹神州細胞因子產(chǎn)品特色以及應用案例03義翹神州細胞因子產(chǎn)品線特點概述GMP認證書250+細胞因子類分子，800+細胞因子類產(chǎn)品按照ISO9001:2015和ISO13485:2016質(zhì)量管理體系要求進行生產(chǎn)覆蓋生長因子，趨化因子，干擾素，白介素，淋巴因子等涉及免疫細胞培養(yǎng)，干細胞研究，類器官培養(yǎng)等熱門應用領域嚴格質(zhì)控造就更優(yōu)細胞活性高批間一致性高純度低內(nèi)毒素（20+GMP級細胞因子）義翹神州細胞因子產(chǎn)品設計種屬多：human、mouse、monkey等，盡可能滿足不同的動物實驗模型傾向于無標簽或者小標簽真核或者原核表達系統(tǒng)內(nèi)毒素低活性有競爭力提供相關應用的解決方案義翹神州細胞因子產(chǎn)品設計多種屬：Human、Mouse、Monkey等，盡可能滿足不同的動物實驗模型的需求義翹神州用于小腸隱窩分離和類器官培養(yǎng)(Lietal.2020)小鼠小腸隱窩富集包埋在Matrigel中接種到24孔板上添加類器官培養(yǎng)基每2天更換新鮮培養(yǎng)基AdvancedDMEM/F12medium50ng/mLMouseEGF(SinoBiological,50482-MNCH)100ng/mLMouseNoggin(SinoBiological,50688-M02H)500ng/mLHumanR-spondin1(SinoBiological,11083-HNAS)培養(yǎng)主要組成細胞因子產(chǎn)品設計低內(nèi)毒素(Sivasubramaniyanetal.2008)LPS處理的胚狀體中胚層的生物標志物會消失且不能分化成有功能的成骨細胞LPS處理的胚狀體會出現(xiàn)凋亡的現(xiàn)象義翹神州細胞因子產(chǎn)品設計提供相關應用的解決方案-1：類器官應用場景iPSC-derivedhumanvascularorganoids(Day7)wereculturedwithFGF2(Cat#10014-HNAE),VEGFA(Cat#11066-HNAH),EGF(Cat#10605-HNAE).Redarrowsrepresentvascularorganoids.Imagetakenat10xmagnification.義翹神州細胞因子產(chǎn)品設計提供相關應用的解決方案-2：免疫細胞應用場景CD14+

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DCs義翹神州高純度血管類器官培養(yǎng)FGF2/bFGF10014-HNAE類器官培養(yǎng)相關產(chǎn)品數(shù)據(jù)iPSC-derivedhumanvascularorganoids(Day7)wereculturedwithFGF2(Cat#10014-HNAE),VEGFA(Cat#11066-HNAH),EGF(Cat#10605-HNAE).Redarrowsrepresentvascularorganoids.Imagetakenat10xmagnification.VEGF16511066-HNAH高純度≥95%義翹神州≥95%類器官培養(yǎng)相關產(chǎn)品數(shù)據(jù)KGF/FGF-750394-M07E小鼠膀胱類器官培養(yǎng)MouseBladderOrganoidsafter14daysinculture.25ng/mLofRecombinantMouseKGF/FGF-7Protein(50394-M07E)wasusedfor2weeksinBMEsubmergedinmousebladdermedia.DataprovidedbyDr.YinatWashingtonUniversity,St.Louis,MO.義翹神州國外知名品牌義翹批次1義翹批次2活性比較數(shù)據(jù)批間一致性數(shù)據(jù)MeasuredinacellproliferationassayusingBalb/C3T3mouseembryonicfibroblasts.EGF10605-HNAE義翹神州批次1義翹神州批次2義翹神州批次3國外知名品牌義翹神州批次1義翹神州批次2(Lietal.2020)腸道類器官腸道類器官培養(yǎng)-文獻中產(chǎn)品應用案例1腸損失后的腸道再生義翹神州小鼠小腸隱窩富集包埋在Matrigel中接種到24孔板上添加類器官培養(yǎng)基每2天更換新鮮培養(yǎng)基AdvancedDMEM/F12medium50ng/mLMouseEGF(SinoBiological,50482-MNCH)100ng/mLMouseNoggin(SinoBiological,50688-M02H)500ng/mLHumanR-spondin1(SinoBiological,11083-HNAS)培養(yǎng)主要組成結(jié)直腸癌類器官腸道類器官培養(yǎng)-文獻中產(chǎn)品應用案例2(Chenetal.2022)義翹神州結(jié)直腸癌患者耐藥性的研究AdvancedDMEM/F12medium50ng/mLMouseEGF(SinoBiological,50482-MNCH)100ng/mLMouseNoggin(SinoBiological,50688-M02H)500ng/mLHumanR-spondin1(SinoBiological,11083-HNAS)培養(yǎng)主要組成結(jié)直腸癌組織分離原代培養(yǎng)包埋在Matrigel中接種到24孔板上添加類器官培養(yǎng)基每3天更換新鮮培養(yǎng)基結(jié)直腸癌類器官用于：藥敏試驗轉(zhuǎn)錄組測序其他類器官培養(yǎng)-文獻中產(chǎn)品應用案例1滋養(yǎng)層類器官(Ruanetal.2022)擴增潛力干細胞-滋養(yǎng)層干細胞來源的滋養(yǎng)層類器官義翹神州50ng/mLHumanHGF(SinoBiological,10463-HNAS)50ng/mLHumanEGF80ng/mLHumanR-spondin1(SinoBiological,11083-HNAS)培養(yǎng)中用到的細胞因子100ng/mLHumanFGF2類器官培養(yǎng)相關產(chǎn)品數(shù)據(jù)義翹神州活性比較數(shù)據(jù)批間一致性數(shù)據(jù)Measuredbyitsabilitytoinduceactivationof?cateninresponseinaTopflashLuciferaseassayusingHEK293Thumanembryonickidneycells.RSPO111083-HNAS國外知名品牌義翹神州義翹神州批次1義翹神州批次2義翹神州批次3活性比較數(shù)據(jù)批間一致性數(shù)據(jù)MeasuredbyitsabilitytoneutralizeTGF-betamediatedinhibitiononMv-1-Lucellproliferation.HGF10463-HNAS義翹神州國外知名品牌義翹神州批次1義翹神州批次2義翹神州批次3(Tangetal.2022)不同時間點顱咽管瘤類器官的形態(tài)

腦腫瘤類器官腦類器官培養(yǎng)-文獻中產(chǎn)品應用案例1義翹神州10ng/mLHumanFGF10(SinoBiological,10573-HNAE)10ng/mLHumanEGF(SinoBiological,10605-HNAE)培養(yǎng)中用到的細胞因子類器官培養(yǎng)相關產(chǎn)品數(shù)據(jù)活性比較數(shù)據(jù)活性比較數(shù)據(jù)CellproliferationassayusingBaF3mousepro-BcellstransfectedwithhumanFGFR2b.CellproliferationassayusingBaF3mousepro-BcellstransfectedwithhumanFGFR2b.義翹神州FGF7/KGF10210-H07EFGF1010573-HNAE≥95%≥95%國外知名品牌義翹神州國外知名品牌義翹神州類器官培養(yǎng)相關產(chǎn)品數(shù)據(jù)

GM