義翹講堂《類器官研究領(lǐng)域快速崛起的“基石”：細(xì)胞因子》

類器官研究領(lǐng)域快速崛起的“基石”：細(xì)胞因子李田子,Ph.D.

高級(jí)產(chǎn)品經(jīng)理北京義翹神州科技股份有限公司05-2024義翹神州CONTENT類器官與細(xì)胞因子1類器官培養(yǎng)的關(guān)鍵細(xì)胞因子“配方”2經(jīng)類器官培養(yǎng)驗(yàn)證的細(xì)胞因子3義翹神州類器官與細(xì)胞因子01義翹神州類器官研究-市場(chǎng)情況義翹神州In2023，TheglobalorganoidsandspheroidsmarketsizewasestimatedatUSD1.1billionCAGR(2024-2032):19.1%Source:ByEnd-UseBiotchenology&PharmaceuticalindustriesAcademic&ResearchinstitutesHospitals&DiagnosticCenters類器官研究-市場(chǎng)情況義翹神州√√√√√HanbyeolLee;etal./10.51335/organoid.2021.1.e11.Paper：NCBI-PubMedCentralClinicaltrials：Organoid-223studies類器官研究-研究進(jìn)展Source:https://ClinicalTUntil05/06/2024RegionNameStudies#World223Europe95NorthAmerica50EastAsia53……Conditionsby

AlphabeticalStudies#DigestiveSystemDiseases90Carcinoma61EndocrineSystemDiseases35UrogenitalDiseases32BreastNeoplasms31……義翹神州類器官研究-潛在應(yīng)用義翹神州Figure.PotentialapplicationsofhumanorganoidsBasicresearch-Cell-to-cellinteractionsMechanismsofstemcellhomeostasisBiobankingDiseasemodeling-Mechanismsofhumandiseases-InheritablegeneticdisordersDrug-screeninganalysesPrecisionmedicine-Responsetodrugs-ResourcesforregenerativemedicinecoupledwithgeneticengineeringJihoonKim;etal./10.1038/s41580-020-0259-3.類器官研究-疾病模型2024年4月24日,Nature刊發(fā)了一篇類關(guān)于腦器官相關(guān)的研究文章Timothy綜合征：自閉癥、神經(jīng)系統(tǒng)問(wèn)題的遺傳性疾病，由CACNA1C基因突變引起。在小鼠模型中，相關(guān)突變并不總是能引起與人類疾病相同的癥狀。類器官解決這一難題。hiPS分化建立hCO，移植到搭上發(fā)育皮層，與其大腦整合。干細(xì)胞（hiPS）：從Timothy綜合征的患者提取獲得hCO：humancorticalorganoids義翹神州XiaoyuChen;etal./10.1038/s41586-024-07310-6

腸道類器官-疾病模型作者感染模型干細(xì)胞來(lái)源Ettayebietal.(2016)HIEsgeneratedfromstemcellsofhumanintestinalcryptsStemcellsisolatedfromintestinalcryptsinhumanintestinaltissuesZhangetal.(2017)HIOsdevelpedfromhumanPSCPSClineWA01(non-secretor)andWA09(secretor)Satoetal.(2017)IECsdevepedfromhumaniPSCHumaniPSCline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(dòng)物模型缺少可用于繁殖這種RNA病毒的的體外細(xì)胞培養(yǎng)系統(tǒng)等問(wèn)題3D腸道類器官挑戰(zhàn)義翹神州HIE:humanintestinalenteroid

IEC:IntestinalepithelialcellsHIO:humanintestinalorganoidJeHyoungKim;etal./10.4167/jbv.2068.腸道類器官-藥物篩選應(yīng)用場(chǎng)景疾病研究題目臨床#藥物篩選結(jié)直腸癌ProspectiveObservationontheAccuracyofinVitroScreeningofColorectalCancerChemotherapyDrugsBasedonOrganoids-ona-chipNCT04996355TheCultureofAdvanced/Recurrent/MetastaticColorectalCancerOrganoidsandDrugScreeningNCT05304741Patient-derivedOrganoidsofRAS/RAFWild-typeMetastaticRightColonCancertoTesttheSensitivityandClinicalConsistencyofCombinedTreatmentofCetuximab.NCT04906733AProspectiveMulticenterRandomizedControlledTrialoftheClinicalEfficacyofNeoadjuvantTherapyBasedonOrganoidsDrugSensitivityVersusEmpiricalNeoadjuvantTherapyintheTreatmentofAdvancedRectalCancerNCT05352165義翹神州QinyingWang;etal./10.1038/s41392-022-01194-6.腦類器官培養(yǎng)過(guò)程腦類器官的培養(yǎng)過(guò)程1.擴(kuò)增誘導(dǎo)多能干細(xì)胞(iPSC)2.放入的基質(zhì)膠(Matrigel)使干細(xì)胞發(fā)育成腦類器官3.培養(yǎng)基中通常加入所需的細(xì)胞因子義翹神州AnaBelénGarcía-Delgado;etal./10.3390/ani12223150.腸道類器官培養(yǎng)過(guò)程類器官培養(yǎng)過(guò)程：(A–C)Afterthestartofcryptculture,theupperopeningrapidlybecomesealed.(D–F)Then,thelumenisfilledwithapoptoticcells.(G,H)Thecryptregionundergoescontinuousbuddingevents.(D–H)Asterisksindicatethelumen.(G,H)Whitearrowsindicatecryptbudding.1.擴(kuò)增小鼠小腸隱窩細(xì)胞，包埋在基質(zhì)膠中2.培養(yǎng)基加入細(xì)胞因子：比如EGF、Noggin和RSPO1義翹神州ToshioTakahashi;etal./10.3390/ijms222010912.類器官培養(yǎng)的關(guān)鍵細(xì)胞因子“配方”02義翹神州BDNF、GDNF中腦類器官FGF2、InsulinVEGFEGF、Noggin腦類器官培養(yǎng)-主要細(xì)胞因子小腦類器官將多能細(xì)胞分化為神經(jīng)外胚層譜系腦類器官生成血管引導(dǎo)細(xì)胞沿特定器官譜系分化分化和成熟義翹神州BenjaminGalet;etal./10.3389/fneur.2020.01005.PraveenJosephSusaimanickam;etal./10.15283/ijsc22006.

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

/10.3389/fncel.2021.646921.腦類器官-疾病模型不同類型腦類器官疾病模型/潛在應(yīng)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(rèn)知功能障礙的潛在模型小腦類器官脊髓小腦共濟(jì)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***義翹神州JayGopalakrishnan./10.1002/bies.201900011.*米勒-迪克綜合征:無(wú)腦回畸形為特征的病癥***蒂莫西綜合癥:一種罕見(jiàn)的多系統(tǒng)遺傳性疾病**丹迪-沃克綜合征:小腦發(fā)育不正常腦類器官培養(yǎng)-主要細(xì)胞因子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ElizabethDiLullo;etal./10.1038/nrn.2017.107.JayGopalakrishnan./10.1002/bies.201900011.RSPO-1EGFNogginWnt腸道類器官培養(yǎng)-主要細(xì)胞因子腸道類器官激活小腸隱窩的Wnt信號(hào)協(xié)助小腸增殖隱窩數(shù)量增多維持腸道干細(xì)胞義翹神州ToshiroSato;etal./10.1053/j.gastro.2011.07.050.腸道類器官-不同種屬培養(yǎng)試劑差異種屬器官干細(xì)胞培養(yǎng)條件BasalculturemediumEGFNogginRSPO-1Wnt3aNicotinamideGastrinA-83-01SB202190MouseSmallintestine√√√√Colon√√√√√HumanSmallintestine√+gastrin√√√√√√√√Colon√+gastrin√√√√√√√√義翹神州ToshiroSato;etal./10.1053/j.gastro.2011.07.050.Figure.Human-derivedorganoids類器官研究-相關(guān)細(xì)胞因子BrainBreastLungProstatePancreaticHeartIntestinalGastricLiverEGFEGFEGFEGFEGFEGFFGF2FGF2FGF2FGF2FGF2FGF2FGF2FGF7TGFB1FGF10FGF10FGF10FGF10FGF10FGF10FGF10NOGNOGNOGNOGNOGNOGNOGNOGINHBAINHBAINHBAINHBAHGFRSPO1RSPO1RSPO1RSPO1RSPO1RSPO1RSPO1OSMDKK1DKK1GDNFLIF義翹神州OVARYBRAINBREASTLUNGSKIDNEYBLADDERPROSTATEEYESINNEREARESOPHAGUSSTOMACHINTESTINEandCOLONLIVERPANCREASBenedettaArtegiani;etal./10.1093/hmg/ddy187.經(jīng)類器官培養(yǎng)驗(yàn)證的細(xì)胞因子03義翹神州細(xì)胞因子產(chǎn)品線特點(diǎn)概述GMP認(rèn)證書(shū)250+細(xì)胞因子類分子，800+細(xì)胞因子類產(chǎn)品按照ISO9001:2015和ISO13485:2016質(zhì)量管理體系要求進(jìn)行生產(chǎn)涉及免疫細(xì)胞培養(yǎng)、干細(xì)胞研究、類器官培養(yǎng)等熱門(mén)應(yīng)用領(lǐng)域覆蓋生長(zhǎng)因子、趨化因子、干擾素、白介素、淋巴因子等嚴(yán)格質(zhì)控造就更優(yōu)細(xì)胞活性高批間一致性高純度（20+GMP級(jí)細(xì)胞因子）義翹神州2024年值得關(guān)注的生長(zhǎng)因子供應(yīng)商細(xì)胞因子產(chǎn)品設(shè)計(jì)種屬多：Human、Mouse、Monkey等，盡可能滿足不同的動(dòng)物實(shí)驗(yàn)?zāi)Ｐ蛢A向于無(wú)標(biāo)簽或者小標(biāo)簽真核或者原核表達(dá)系統(tǒng)低內(nèi)毒素活性有競(jìng)爭(zhēng)力應(yīng)用場(chǎng)景數(shù)據(jù)展示義翹神州細(xì)胞因子產(chǎn)品設(shè)計(jì)多種屬：Human、Mouse、Monkey等，盡可能滿足不同的動(dòng)物實(shí)驗(yàn)?zāi)Ｐ偷男枨罅x翹神州用于小腸隱窩分離和類器官培養(yǎng)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YuanchuangLi;etal./10.1016/j.stemcr.2020.12.005.細(xì)胞因子產(chǎn)品設(shè)計(jì)低內(nèi)毒素LPS處理的胚狀體中胚層的生物標(biāo)志物會(huì)消失且不能分化成有功能的成骨細(xì)胞LPS處理的胚狀體會(huì)出現(xiàn)凋亡的現(xiàn)象義翹神州KavithaSivasubramaniyan;etal./10.2217/1746073.細(xì)胞因子產(chǎn)品設(shè)計(jì)應(yīng)用場(chǎng)景數(shù)據(jù)展示-1：類器官應(yīng)用場(chǎng)景義翹神州產(chǎn)品詳情頁(yè)下拉點(diǎn)開(kāi)產(chǎn)品詳情頁(yè)細(xì)胞因子產(chǎn)品設(shè)計(jì)應(yīng)用場(chǎng)景數(shù)據(jù)展示-2：免疫細(xì)胞應(yīng)用場(chǎng)景CD14+

monocytes

were

differentiated

into

immature

DCs

by

GM-CSF(GMP-10015-HNAH)

and

IL4(GMP-11846-HNAE)

for

6

days.

DCs

were

matured

by

TNF(GMP-10602-HNAE)

for

2

days.Immature

DCsMature

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(guān)產(chǎn)品數(shù)據(jù)iPSC-derivedhumanvascularorganoids(Day7)wereculturedwithFGF2(10014-HNAE),VEGF165(11066-HNAH),EGF(10605-HNAE).Redarrowsrepresentvascularorganoids.Imagetakenat10xmagnification.VEGF16511066-HNAH高純度≥95%義翹神州≥95%類器官培養(yǎng)相關(guān)產(chǎn)品數(shù)據(jù)KGF/FGF-750394-M07E小鼠膀胱類器官培養(yǎng)MouseBladderOrganoidsafter14daysinculture25ng/mLofRecombinantMouseKGF/FGF-7Protein(50394-M07E)

wasusedfor2weeksinBMEsubmergedinmousebladdermedia.DataprovidedbyDr.YinatWashingtonUniversity,St.Louis,MO.義翹神州國(guó)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(guó)外知名品牌義翹神州批次1義翹神州批次2經(jīng)過(guò)14天的培養(yǎng)腸道類器官腸道類器官培養(yǎng)-文獻(xiàn)中產(chǎn)品應(yīng)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YuanchuangLi;etal./10.1016/j.stemcr.2020.12.005.結(jié)直腸癌類器官腸道類器官培養(yǎng)-文獻(xiàn)中產(chǎn)品應(yīng)用案例2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(yàn)轉(zhuǎn)錄組測(cè)序LifengChen;etal./10.3389/fonc.2022.855674.其他類器官培養(yǎng)-文獻(xiàn)中產(chǎn)品應(yīng)用案例滋養(yǎng)層類器官擴(kuò)增潛力干細(xì)胞-滋養(yǎng)層干細(xì)胞來(lái)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(xì)胞因子100ng/mLHumanFGF2DegongRuan;etal./10.1016/j.xcrm.2022.100849.類器官培養(yǎng)相關(guān)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(guó)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(guó)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不同時(shí)間點(diǎn)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(xiàn)中產(chǎn)品應(yīng)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(xì)胞因子X(jué)iao-YanTang;etal./10.1038/s41392-022-01024-9.類器官培養(yǎng)相關(guān)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(guó)外知名品牌義翹神州國(guó)外知名品牌義翹神州類器官培養(yǎng)相關(guān)產(chǎn)品數(shù)據(jù)

InhibitproliferationofMPC-11cells.>1000U/mgCellproliferationassayusingTF-1humanerythroleukemiccells.>30,000Units/μg≥95%≥95%活性比較數(shù)據(jù)批間一致性數(shù)據(jù)義翹神州義翹神州國(guó)外知名品牌義翹神州批次1義翹神州批次2

GMP級(jí)HumanActivinAGMP-10429-HNAH

GMP級(jí)HumanOSMGMP-10452-HNAH經(jīng)不同類器官培養(yǎng)驗(yàn)證的細(xì)胞因子義翹神州人腸癌類器官人結(jié)直腸類器官HumanintestinalcancerorganoidswereculturedwithRSPO1(11083-HNAS),EGF(50482-MNCH),NOG(50688-M02H).(Routinelytested).DataprovidedbyD1MedicalTechnologyHumancolorectumorganoidswereculturedwithRSPO1(11083-HNAS),EGF(50482-MNCH),NOG(50688-M02H).(Routinelytested).DataprovidedbyD1MedicalTechnology.義翹神州人肺癌類器官人肺類器官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.經(jīng)不同類器官培養(yǎng)驗(yàn)證的細(xì)胞因子義翹神州人肝癌類器官人膽管癌類器官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.經(jīng)不同類器官培養(yǎng)驗(yàn)證的細(xì)胞因子義翹神州人腎癌類器官人腎類器官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.經(jīng)不同類器官培養(yǎng)驗(yàn)證的細(xì)胞因子義翹神州人胃癌類器官人胃類器官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