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Li-Hepatocyte ho Metabolism ea Lithethefatsi le SiRNA Phano ea Lithethefatsi: Ho lekola Mekhoa ea Mehlala ho Mefuta Eohle

Mantsoe a bohlokoa: Li-Hepatocyte, Li-Hepatocyte tse ka Sehloohong, Li-Hepatocyte Tse Plateable, Li-Hepatocyte Tse Emisoang, Hepatocytes Metabolic Stability, Hepatotoxicity, CYP450 Enzyme Induction, Primary Human Hepatocytes(PHH), Primary Cynomolgus Monkey Hepatocytes(PCH) , Animal Hepatocytes Hepatocytes, Plate Human Hepatocytes Hepatocytes , Plateable Rhesus Monkey Hepatocytes, Plateable Dog Hepatocytes, Plateable Beagle Hepatocytes, Plateable Sprague-Dawley Rat Hepatocytes, Plateable ICR/CD-1 Mouse Hepatocytes, Plateable C57BL/6 Mouse Hepatocytes, Plateable Hepatocytes Syria, Plateable Hepatocytes Minipig Hepatocytes, Plateable New Zealand White Rabbit Hepatocytes, Plateable Chicken Hepatocytes, Suspension Human Hepatocytes, Suspension Cynomolgus Monkey Hepatocytes, Suspension Rhesus Monkey Hepatocytes, Suspension Dog Hepatocytes, Suspension Beagle Hepatocytes Hepatocytes Hepatocytes Hepatocytes Hepatocytes Wistar Rat Hepatocytes,Suspension Wistar Han Rat Hepatocytes,Suspension ICR/CD-1 Mouse Hepatocytes, Suspension C57BL/6 Mouse Hepatocytes, Suspension Golden Syrian Hamster Hepatocytes, Suspension Feline Hepatocytes, Suspension Minipig Hepatocytes, Suspension Hepatocytes New Zealand White RatASGPR, GalNAC-siRNA, Primary Hepatocyte siRNA Transfection siRNA Galnac Hepatocyte Delivery,Phepelo e Lebisitsoeng ho Hepatic.

Lebitso la Sehlahiswa

Tlhaloso

Ho fanyeha Li-Hepatocyte tsa Mantlha

 

IPHASE Suspension Human Primary Hepatocytes

4 - limilione tse 6

IPHASE Suspension Monkey(Cynomolgus) Hepatocytes,Male

5 limilione

IPHASE Suspension Monkey(Rhesus) Hepatocytes,Male

5 limilione

IPHASE Suspension Dog(Beagle) Hepatocytes,E tona

5 limilione

IPHASE Suspension Rat(Sprague-Dawley) Hepatocytes,Male

5 limilione

IPHASE Suspension Rat(Wistar) Hepatocytes,Male

5 limilione

IPHASE Suspension Rat(Wistar Han) Hepatocytes,Male

5 limilione

IPHASE Suspension Mouse(ICR/CD-1) Hepatocytes,Male

5 limilione

IPHASE Suspension Mouse(C57BL/6) Hepatocytes,Male

2 limilione

IPHASE Suspension Hamster(Golden Syrian) Hepatocytes,Male

5 limilione

IPHASE Suspension Feline Hepatocytes,Bong bo Kopantsoeng

5 limilione

IPHASE Suspension Minipig(Bama) Hepatocytes,Male

5 limilione

IPHASE Suspension Rabbit(New Zealand White) Hepatocytes,Male

5 limilione

IPHASE Suspension Broiler Chicken Hepatocytes,Male

2 limilione

Plateable Primary Hepatocyte

 

IPHASE Plateable Human Primary Hepatocytes,Male

4 - limilione tse 6

IPHASE Plateable Human Primary Hepatocytes,Mosali

4 - limilione tse 6

IPHASE Plateable Monkey(Cynomolgus) Hepatocytes,Male

5 limilione

IPHASE Plateable Monkey(Rhesus) Hepatocytes,Male

5 limilione

IPHASE Plateable Dog(Beagle) Hepatocytes,E tona

5 limilione

IPHASE Plateable Rat(Sprague-Dawley) Hepatocytes,Male

5 limilione

IPHASE Plateable Mouse(ICR/CD-1) Hepatocytes,Male

5 limilione

IPHASE Plateable Mouse(C57BL/6) Hepatocytes,Male

5 limilione

IPHASE Plateable Feline Hepatocytes,Male

5 limilione

IPHASE Plateable Minipig(Bama) Hepatocytes,Male

5 limilione

IPHASE Plateable Rabbit(New Zealand White) Hepatocytes,Male

5 limilione

IPHASE Plateable Rabbit(Japanese White) Hepatocytes,E tona 5 limilione

Lisebelisoa

 

IPHASE Human Hepatocyte Thaw Medium

50mL

IPHASE Mouse Hepatocyte Thaw Medium

40mL

IPHASE Animal Hepatocyte Thaw Medium

10mL

IPHASE Hepatocyte Incubation Medium

10mL

IPHASE Hepatocyte Plateable Medium

20mL

IPHASE Hepatocyte Maintenance Medium

50mL

IPHASE Collagen Coated Plate, liliba tse 96

96 Liliba/1 li-blocks

IPHASE Collagen Coated Plate, liliba tse 48

48 Liliba/1 li-blocks

IPHASE Collagen Coated Plate, liliba tse 24

24 Liliba/1 li-blocks

IPHASE Collagen Coated Plate, liliba tse 12

12Liliba/5 Lipoleiti

IPHASE Collagen Coated Plate, 6 liliba

6 Liliba/1 li-blocks

IPHASE Human Hepatocytes mRNA Induction Assay Kit

100 maikutlo

IPHASE Primary Hepatocytes Isolation Kit

1Set

Tlhokomeliso: The Suspension Hepatocyte lokela ho sebelisoa le Thaw Medium le Incubation Medium; Plateable Hepatocyte e hloka ho sebelisoa le Thaw Medium, Plateable Medium, Maintenance Medium, le Collagen Coated Plate. Ho kenngoa ha CYP ho hloka mRNA Induction Assay Kit hape.

Hepatocytes

Hepatocyteske lisele tse ka sehloohong tse sebetsang ka har'a sebete, tse bapalang karolo e ka sehloohong metabolism, detoxification, tlhahiso ea bile, le protheine synthesis. Li theha motheo oa sebopeho le lik'hemik'hale tsa ts'ebetso ea sebete, li sebetsa e le bakena-lipakeng ba ka sehloohong phetohong ea metsoako e fapaneng ea endogenous le exogenous hore e be lintho tse seng kotsi haholo le ho thusa metabolism ea lithethefatsi le chefo. Bokhoni bona ba tlhaho ba hepatocyte ba ho sebetsana le lik'hemik'hale bo entse hore e be tsa bohlokoa haholo litsing tsa bongaka le tsa lipatlisiso, haholo ha ho etsoa lipatlisiso ka litsela tse amehang ho metabolism ea lithethefatsi le chefo ea sebete.

Hepatocyte ea mantlha

Li-hepatocyte tsa mantlha li bua ka lisele tse sa tsoa aroloa ho lisele tsa sebete-ebang ke motho kapa phoofolo-ntle le ho ata ha nako e telele ka in vitro. Hobane lisele tsena li boloka boholo ba tšebetso ea enzymatic le tšebetso ea fisioloji eo e leng tšobotsi ea sebete, hangata li nkuoa e le maemo a khauta lithutong tse hlahlobang sebete-mesebetsi e khethehileng. Tšebeliso ea bona lipatlisisong e bohlokoa ho utloisisa botsitso ba metabolic le matla a kahare a lithethefatsi hore a fetohe kapa a tsoelepele ka sebopeho sa ona sa mantlha hang ha a se a kentsoe tsamaisong ea baeloji.

Li-Hepatocyte tse Plateable le Li-Hepatocyte tse emisitsoeng

Ka har'a meralo ea liteko, li-hepatocyte li ka aroloa ho latela maemo a tsona a ho lema. Li-hepatocyte tse nang le plateable ke tse khomarelang motsoako oa setso, o lumellang hore ho be le sehokelo se tsitsitseng le morphology e etsisang tikoloho ea vivo haufi-ufi. Sehokelo sena ha se tšehetse feela sebopeho sa polarized ea lisele tsena empa hape se ts'ehetsa lithuto tsa nako e telele tsa litsela tsa biochemical joalo kaHo kenngoa ha enzyme ea CYP450. Ka lehlakoreng le leng, li-hepatocyte tse emisitsoeng li bolokiloe sebakeng se sa lumellaneng, ka tloaelo se sebelisoa ka nako e khutšoanyane ea litlhahlobo moo liphetoho tsa tikoloho ea cellular le litlhahlobo tse potlakileng tsa metabolism li hlokahalang. Litloaelo tse emisitsoeng li thusa ho pepeseha ka mokhoa o ts'oanang ha lisele ho etsa liteko tsa metsoako, e leng se etsang hore e be tse loketseng bakeng sa litlhahlobo tse potlakileng tsa botsitso ba metabolism le likarabo tse matla tsa hepatotoxic.

Li-Hepatocyte tse ka tšeptjoang

Li-hepatocyte tse ka tšeptjoangke lisele tsa sebete tse arohaneng tse hlahisitsoeng ka lijana tse koahetsoeng kapa tse khethehileng tsa setso. Sehokelo sena se lumella lisele hore li hasane, li arole, 'me li thehe likhokahano tsa li-intercellular, li boloke mesebetsi e mengata e kang ea vivo ka matsatsi a' maloa kapa libeke. Hobane lisele tsena li khomarela, li ka sebelisoa ho lekola likarabo tse sa foleng, ho kenngoa ha enzyme ea CYP450 ha nako e ntse e ea, le liteko tsa chefo ea matsatsi a mangata. Li-hepatocyte tse nang le li-plateable li boetse li boloka lisele tse matla - ho - lisele tsa puisano le likamano tsa matrix tsa extracellular, tse bohlokoa bakeng sa ho boloka sebete - ts'ebetso e khethehileng. Mofuta o mong le o mong—ebang ke oa motho, oo e seng oa batho, oa litoeba, kapa o mong—o ka hloka maemo a ntlafalitsoeng (joalo ka liphahlo tse itseng kapa lisebelisoa tsa mecha ea litaba) ho etsa hantle maemo a bophelo.

Ho emisoa ha Hepatocyte

Ho fapana le hoo,Ho emisa li-hepatocyteba hōlile ka mokhoa o sa lumellaneng, ba boloka sebopeho se pota-potileng ha ba ntse ba sebetsa ka nako e khutšoanyane. Li-hepatocyte tse emisitsoeng li loketse bakeng sa liteko tsa nako e khuts'oane, joalo ka lithuto tsa pele tsa metabolism ea lithethefatsi kapa litlhahlobo tse potlakileng tsa enzyme kinetics. Kaha lisele ha li thibetsoe ke li-attachments tsa matrix, li ka lokisoa ka potlako le ho sebelisoa bakeng sa liteko tsa ts'ebetso ntle le tieho e hlokahalang bakeng sa ho khomarela lisele. Litloaelo tse emisitsoeng li bohlokoa haholo ha li bapisa mefuta e fapaneng ea mefuta, kaha li lumella litlhahlobo tse potlakileng ho pholletsa le Suspension hepatocyte ho tsoa ho batho, bao e seng litšoene, litoeba le mefuta e meng.

Ho tsitsa ha metabolism le Hepatotoxicity

Ho tsitsa ha metabolismmoelelong oa lipatlisiso tsa hepatocyte e bua ka bokhoni ba molek'hule, hangata e le moemeli oa lithethefatsi, ho hanela phetoho ea lik'hemik'hale ka li-enzyme tsa sebete. Ho batlisisa botsitso ba metabolism ka li-hepatocyte ho lumella bafuputsi ho bolela esale pele halofo - bophelo le lihlahisoa tse ka 'nang tsa senyeha tsa lintho tsena, tse bohlokoa ho nts'etsopele ea lithethefatsi. Boemo ba metabolic ba komporo ha bo bone feela hore na bo sebetsa hantle hakae empa le polokeho ea eona, kaha ka linako tse ling metabolite e ka hlahisa litlamorao tse chefo tse sa bonoeng motsoakong oa motsoali.

Hepatotoxicity, ka lehlakoreng le leng, e akarelletsa liphello tse senyang tsa lik’hemik’hale liseleng tsa sebete. Tšebeliso ea li-hepatocyte tsa mantlha le tse tsoetseng pele lithutong tsa chefo e thusa ho hlakisa mekhoa e lebisang ho lematsa sebete. Sena se bohlokoa hobane sebete, kaha ke setho se bohareng sa metabolism, se hlaseloa habonolo ke mahlapa a chefo a tsoang ho lik'hemik'hale tsa tikoloho le lisebelisoa tsa meriana. Liphuputso tse sebelisang lisele tsena li ka lemoha mekhoa ea ho senyeha ha lisele kapa ho se sebetse hantle, ho fana ka lintlha tsa liketsahalo tsa pele tsa kotsi ea sebete le ho thusa ho bolela esale pele liphello tse mpe maemong a kliniki.

Ho kenngoa ha enzyme ke karolo e 'ngoe ea bohlokoa e amanang le ts'ebetso ea hepatocyte, e buang ka mokhoa oo ka oona lintho tse itseng li eketsang motsoako oa lithethefatsi-metabolism ea li-enzyme. Ketsahalo ena e bohlokoa ka ho khetheha kaha e ka lebisa ho eketseha ha metabolism ea lithethefatsi tse tsamaisoang ka kopanelo, tse ka fokotsang matla a tsona kapa ho eketsa tlhahiso ea metabolite e kotsi. Lipatlisiso tse sebelisang li-hepatocyte tse nang le plateable hangata li reretsoe ho hlahloba litsela tsa taolo tse laolang ho kenngoa ha enzyme, ka hona ho fana ka leseli mabapi le likamano tse rarahaneng pakeng tsa mefuta e sa tšoaneng ea xenobiotics le matla a metabolism a sebete.

Maano a Phano le a Targete ea SiRNA ea Hepatic

Tsoelo-pele ea morao-rao litabeng tsa phekolo ea RNA interference (RNAi) e hlahisitse mekhoa e mecha ea hophano e lebisitsoeng ho hepaticho sebelisa li-RNA tse nyenyane tse sitisang (siRNAs). Mokhoa o ka sehloohong o kenyelletsa ho kopanya limolek'hule tsa siRNA le N-acetylgalactosamine (GalNAc), e thusang ho khethoa ha li-hepatocyte ka asialoglycoprotein receptor (ASGPR). ASGPR e hlahisoa haholo holim'a li-hepatocyte 'me e phetha karolo ea bohlokoa ho kenngoa ha endocytic ka hare.GalNAc-siRNAconjugates, e leng se etsang hore e be tsela ea bohlokoa bakeng sa sebete-ho fana ka lithethefatsi tse khethehileng.

Lithuto tsa in vitro hangata li sebelisoaPhetolelo ea mantlha ea Hepatocyte siRNAmekhoa ea ho hlahloba bokhoni le boits'oaro basiRNA GalNAc Hepatocyte Delivery. Mekhoa ena e lumella bafuputsi ho ithuta ka litlamorao tsa liphatsa tsa lefutso maemong a amanang le 'mele le ho ntlafatsa mekhoa ea ho fana ka li-intracellular le ho khutsisa liphatsa tsa lefutso.

Ka kakaretso, Hepatic Targeted Delivery of RNA therapeutics using ASGPR-mediated GalNAc-siRNA systems e emela mokhoa o tobileng haholo le o seng oa kokoana-hloko oa ho phekola mafu a lefutso a sebete le mathata a metabolic, ho matlafatsa ka ho eketsehileng tšebeliso ea mehlala ea mantlha ea hepatocyte lipatlisisong tsa phetolelo le nts'etsopele ea lithethefatsi.

Mefuta- Lintlha tse khethehileng tsa Hepatocyte

Hepatocyte ea batho

Li-Hepatocyte tsa Batho tse Plateable li bohlokoa bakeng sa ho bolela esale pele metabolism ea lithethefatsi tsa motho le chefo, e fanang ka bohlokoa bo phahameng ba ts'ebetso. Ho khomarela lipoleiti tse khethehileng ho lumella ho ithuta ka ho kenngoa ha enzyme ea metabolic, metabolism ea phase I / II, le mosebetsi oa lipalangoang.

Ka mokhoa o sa lumellaneng,Ho fanyeha li-hepatocytes tsa motho arabela ka potlako ho xenobiotics, e leng se etsang hore e be tse loketseng bakeng sa litlhahlobo tse potlakileng tsa metabolism, lithuto tsa ho hlakola, le tlhahlobo ea nakoana ea chefo.

E seng - Li-Hepatocyte tsa Motho

Ho tšoana ha fisioloji le batho ho etsaPlateable Cynomolgus Monkey HepatocyteslePlateable Rhesus Monkey Hepatocytes ea bohlokoa bakeng sa ho kopanya lithuto tsa pele ho bophelo ka liphetho tsa batho. Li sebelisetsoa ho lekola metabolism ea lithethefatsi, tlhahiso ea li-enzyme, le mefuta - profaele e khethehileng ea polokeho.

Cynomolgus ea ho emisoa Litšoene tsa HepatocyteleHo emisoa ha Rhesus Monkey Hepatocytes etsa hore ho be le litekanyetso tse potlakileng, tse bapisoang tsa mesebetsi ea metabolism le likarabo tse matla, tse molemo ha ho hlokahala data ea nako e khuts'oane pele ho nako e telele

Hepatocyte ea Canine

E sebelisoa haholo lipatlisisong tsa bongaka ba liphoofolo le phetolelo,Plateable Ntja HepatocytelePlateable Beagle Hepatocytesetsisa ho fisioloji ea sebete ea vivo ho ithuta lithethefatsi- kotsi e bakoang ke sebete le metabolism ea meriana ea bongaka ba liphoofolo.

Tsena li fana ka liphuputso tse potlakileng tsa metabolism 'me li sebelisoa litekong tsa pele- tsa tlhahlobo ea mothati, tse u ruang molemo ho tsoa ho phallo e potlakileng ea mohlala oa Suspension.

Sprague-Dawley Rat Hepatocytes

TsenaPlateable Sprague-Dawley Rat Hepatocytesli qheletsoe ka thoko ho litoeba tsa Sprague - Dawley mme li ruiloe ka mokhoa o khomaretseng kapa o bonolo. Ka mokhoa oa Plateable, lisele li ikamahanya le sejana sa setso, se li lumellang hore li thehe litšebelisano tse tsitsitseng tsa intercellular le ho boloka sebete-mesebetsi e khethehileng ka nako e telele. Sebopeho sena se loketse ka ho khetheha bakeng sa ho ithuta mekhoa ea nako e telele ea metabolism, ho kenngoa ha enzyme, le litlhahlobo tse sa foleng tsa chefo ho sebelisa lisele tsa sebete sa Sprague-Dawley rat.

Ha e hlokometsoe boemong bo sa lumellaneng,Ho emisoa ha Sprague-Dawley rat hepatocytesli sebelisoa haholo-holo bakeng sa liteko tsa nako e khuts'oane. Sebopeho sa Suspension se thusa litlhahlobo tse potlakileng, joalo ka lithuto tse matla tsa metabolism ea lithethefatsi le litlhahlobo tsa enzyme kinetics, moo ho hlokahalang likarabo tsa ts'ebetso hanghang. Mokhoa ona o molemo ha o bapisa likarabo tse matla tsa metabolic lipakeng tsa mefuta kapa maemo a fapaneng.

ICR/CD-1 Mouse Hepatocytes

E arohane le ICR/CD-1 litoeba, tsena Plateable ICR/CD-1 Mouse Hepatocyteskhomarela sejana sa setso, se ba lumella ho boloka mesebetsi ea bohlokoa ea sebete ka nako e telele. Bafuputsi ba rata mokhoa oa Plateable bakeng sa ICR/CD-1 mouse hepatocytes ha nako e tsitsitseng, e atolositsoeng ea setso e hlokahala bakeng sa litebello tsa liteko.

Ka lehlakoreng le leng, Suspension ICR/CD-1 mouse hepatocytes e ruiloe ntle le ho khomarela, kahoo ho boloka morphology e chitja e loketseng lithuto tsa nako e khutšoanyane -Ho emisa ICR/CD-1 Mouse Hepatocytese lumella tlhahlobo e potlakileng ea likarabelo tsa metabolic 'me e thusa haholo tlhahlobong ea pele kapa ha ho hlokahala tlhahlobo e phahameng - Tšebeliso ea li-hepatocyte tsa Suspension ho ICR / CD- 1 litoeba li thusa ho potlakela ho theha litlaleho tsa motheo tsa metabolism le ho li bapisa le mefuta e meng kapa maemo a fapaneng a liteko.

Likokoana-hloko tsa Hepatocyte

Sebopeho sa Plateable se bohlokoa haholo lithutong tsa nako e telele tse hlokang sebete-mesebetsi e khethehileng, joalo ka liteko tsa chefo e sa foleng le liteko tsa ho kenya li-enzyme. Lithutong tse tsepamisitseng maikutlo ho mafu a sebete sa feline, lithethefatsi- kotsi ea sebete, le mathata a metabolism a khethehileng ho likatse,Li-Hepatocyte tsa Cat e nang le Plateablefana ka mohlala o matla. Ho khomarela ha bona ho boetse ho matlafatsa ho ikatisa ha lintlha tsa morphological le tsa ts'ebetso, ho li etsa mohlala o ratoang ho pharmacology ea bongaka ba liphoofolo le lipatlisiso tsa hepatology.

Sebopeho sa Suspension se thusa ho lekanya likarabelo tsa hang-hang tsa cellular ho xenobiotics, moo ho haella ha sehokelo ho fokotsang tieho ea karabo e bonoang litsong tse telele-litso tsa nako e telele.Ho fanyeha Cat Hepatocytes ka hona li bohlokoa bakeng sa ho tseba liphetoho tsa pele tsa biochemical le litlamorao tse ka bang teng kamora ho pepesetsoa metsoako e mecha.

Hepatocyte ea khoho

Joaloka baemeli ba mefuta ea linonyana,Plateable Chicken Hepatocytesli sebelisoa lithutong tsa papiso ho utloisisa phapang ea ho iphetola ha lintho mesebetsing ea sebete, haholo-holo litekong tsa endocrine disruptor.

Ho fanyeha Chicken Hepatocytese etsa hore lithuto tse potlakileng, tse mahlonoko - tsa metabolism ea sebete ho linonyana 'me li ka bapisoa ka kotloloho le tse ling tsa liphoofolo tse anyesang.

Mefuta e meng

Bakeng sa mefuta e meng, Plateable Minipig Hepatocytes, Ho emisoa Minipig Hepatocytes, Plateable New Zealand White Rabbit Hepatocytes, Suspension New Zealand White Rabbit Hepatocytes,Suspension Wistar Rat Hepatocytes,Suspension Wistar Han Rat Hepatocytes kaofela ke mehlala e tloaelehileng ea ho bolela esale pele le ho hlalosa lithethefatsi-ho sebelisana le lithethefatsi le ho ithuta ka cytotoxicity ea lithethefatsi..

Qetello

Li-hepatocyte li bapala karolo ea bohlokoa ho boloka tšebetso ea sebete ka metabolism, detoxification, tlhahiso ea bile le protheine synthesis. Sengoloa se totobatsa phapang lipakeng tsa li-hepatocyte tsa mantlha le mefuta ea tsona ea setso-li-plateable le li-suspension hepatocyte-e 'ngoe le e' ngoe e ntlafalitsoe bakeng sa merero e fapaneng ea liteko. Li-hepatocyte tse nang le plateable, ka ho khomarela le ho phela nako e telele, li bohlokoa bakeng sa ho ithuta liphello tse sa foleng, ho kenngoa ha enzyme, le mekhoa ea nako e telele ea metabolism, ha li-hepatocyte tse emisitsoeng li fana ka maemo a ho hlahloba ka potlako le a tšoanang bakeng sa litlhahlobo tse matla. Ho phaella moo, tlhahlobo e fetela ho mefuta - lits'ebetso tse khethehileng, tse bontšang kamoo mefuta e fapaneng ea hepatocyte-ho tloha ho batho ho ea ho liphoofolo-lithuso tsa ho bolela esale pele metabolism ea lithethefatsi, ho hlahloba hepatotoxicity, le ho rala mekhoa ea phekolo e lebisitsoeng e kang RNA - mekhoa e thehiloeng ho sebelisa GalNAc conjugation. Tlhaloso ena e pharaletseng e bonts'a karolo ea bohlokoa ea li-hepatocyte lipatlisisong tsa bongaka le nts'etsopele ea meriana, ho fana ka lintlha tsa bohlokoa mabapi le physiology ea sebete le mekhoa e tšehetsang ts'ireletso le katleho ea lithethefatsi.

 

 

 


Nako ea poso: 2025-04-15 10:57:26
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