Hepatocytes ee dheef-shiid kiimikaadka daawada iyo gaarsiinta dawooyinka siRNA: Qiimaynta Nidaamyada Model ee noocyada kala duwan

Erayada furaha: Hepatocytes, Hepatocytes Asaasiga ah, Hepatocytes Plateable, Hepatocytes Hepatocytes, Joojinta Hepatocytes, Hepatocytes Hepatocytes Xasiloonida dheefshiidka, Hepatotoxicity, CYP450 Enzyme Induction, Primary Human Hepatocytes(PHH), Primary Cynomolgus Daanyeer Hepatocytes (PCH) , Hepatocytes Rhesus daayeer Plateable, Hepatocytes eey Plateable, Plateable Hepatocytes Hepatocytes, Plateable Sprague-Dawley Rat Hepatocytes, Plateable ICR/CD- Hepatocytes bakayle, Hepatocytes Digaagga Plateable, Cagaarshow Aadanaha Joojin, Joojinta Cynomolgus Daanyeer Hepatocytes, Joojinta Rhesus Daanyeer Hepatocytes, Joojinta Hepatocytes Hepatocytes, Joojinta Hepatocytes Hepatocytes, Joojinta Sprague-Dawley Rat Hepatocytes ICR / CD-ASGPR, GalNAC-siRNA, Hepatocyte Aasaasiga ah siRNA Gudbinta Cagaarshowga Galnac,Gaarsiinta Hepatic Bartilmaameedka.

Fiiro gaar ah: Hepatocytes-ka-joojinta waxay u baahan yihiin in lagu isticmaalo Dhexdhexaadiyaha Thaw iyo Dhexdhexaadinta Dhexdhexaadinta; Hepatocytes-ka la daabici karo waxay u baahan yihiin in lagu isticmaalo Thaw Medium, Dhexdhexaad la dahaaran karo, Dhexdhexaad Dayactirka, iyo Saxan Dahaarka leh ee Collagen. Soo saarista CYP waxay sidoo kale u baahan tahay Qalabka Induction Assay Kit sidoo kale.

Hepatocytes

Hepatocyteswaa unugyada asaasiga ah ee shaqada beerka, oo ka ciyaara doorka dhexe ee dheef-shiid kiimikaad, sun-saarid, wax-soo-saarka bile, iyo isku-darka borotiinka. Waxay sameeyaan saldhigga qaab-dhismeedka iyo kiimikaad ee shaqada beerka, iyaga oo u dhaqma sida dhexdhexaadiyeyaasha ugu muhiimsan ee u beddelashada xeryahooda kala duwan ee endogenous iyo dibadda u ah walxaha waxyeellada yar iyo fududaynta dheef-shiid kiimikaadka daroogada iyo sunta. Awoodda asaasiga ah ee hepatocytes si ay u farsameeyaan kiimikooyinka ayaa ka dhigtay lagama maarmaanka ah goobaha caafimaadka iyo cilmi-baarista, gaar ahaan marka la baarayo waddooyinka ku lug leh dheef-shiid kiimikaadka daroogada iyo sunta beerka.

Hepatocytes aasaasiga ah

Hepatocytes-ka aasaasiga ah waxay tixraacaan unugyada dhawaan ka go'doonsan unugyada beerka-ha ahaadeen dad ama xayawaan-haddii aan sii dheerayn faafinta vitro. Sababtoo ah unugyadani waxay hayaan in badan oo ka mid ah dhaqdhaqaaqa enzymatic iyo hawlaha jireed ee sifada beerka, inta badan waxaa loo tixgeliyaa heerka dahabka ee daraasadaha baarista beerka-waxqabadyada gaarka ah. Isticmaalkooda cilmi-baadhistu waxay laf-dhabar u tahay fahamka xasilloonida dheef-shiid kiimikaadka iyo awoodda asaasiga ah ee dawooyinka si ay isbeddel ugu sameeyaan ama u sii wataan qaabkoodii asalka ahaa marka la soo geliyo nidaamka noolaha.

Hepatocytes ee la daabi karo iyo Hepatocytes oo Joojin

Qaab-dhismeedka tijaabada ah, hepatocytes waa la sii kala saari karaa iyadoo lagu salaynayo xaaladahooda dhaqan. Hepatocytes ee la dhejin karo waa kuwa ku dheggan substrate dhaqameed, kaas oo u oggolaanaya ku-xirnaansho deggan iyo qaab-dhismeedka kaas oo si dhow ula mid ah deegaanka vivo. Lifaaqani kaliya maaha inuu taageero qaab-dhismeedka kala duwan ee unugyadan laakiin sidoo kale wuxuu sii wadaa daraasado dheer -Induction CYP450. Taa beddelkeeda, ka joojinta hepatocytes-ka waxaa lagu hayaa xaalad aan-a raacsanayn, sida caadiga ah loo isticmaalo shaybaar gaaban - Dhaqamada ka joojinta waxay fududeeyaan soo-gaadhista isku midka ah ee unugyada si ay u tijaabiyaan isku-dhafka, iyaga oo ka dhigaya kuwo ku habboon qiimaynta degdegga ah ee xasilloonida dheef-shiid kiimikaadka iyo jawaabaha cagaarshow ba'an.

Hepatocytes ee la dhejin karo

Hepatocytes ee la dhejin karowaa unugyo beerka oo go'doonsan oo lagu dhaqay suxuunta dhaqameed ee dahaarka leh ama kuwa gaarka ah. Lifaaqan wuxuu u oggolaanayaa unugyadu inay fidaan, kala beddelaan, oo ay samaystaan ​​xidhiidho unugyo dhexdood ah, iyaga oo ilaalinaya qaar badan oo ku jira vivo-shaqo la mid ah maalmo ama xitaa toddobaadyo. Sababtoo ah unugyadani waa kuwo ku dheggan, waxaa loo isticmaali karaa in lagu kormeero jawaabaha daba-dheeraada, CYP450 induction enzyme induction ka dib, iyo maalmo badan oo suntan ah. Hepatocytes ee la samaysan karo waxay sidoo kale ilaalisaa unug aad u adag Nooc kasta -ha ahaato bini'aadmi, mid aan-dabiiciga ah, jiirka, ama kuwa kaleba-waxaa laga yaabaa inay u baahdaan xaalado dahaadh la hagaajiyay (sida dahaarka gaarka ah ama kaabisyada warbaahinta) si ay sida ugu wanaagsan ugu soo celiyaan xaaladaha jireed.

Joojinta Hepatocytes

Taas beddelkeeda,Joojinta hepatocyteslagu dhaqmo si aan -aqoon lahayn, iyagoo ilaalinaya qaab-dhismeedka wareegsan inta ay sii jiri karaan muddo gaaban. Hepatocytes-ka-joojintu waxay ku habboon yihiin tijaabooyinka muddada-gaaban, sida daraasaadka dheef-shiid kiimikaad ee daroogada ama qiimaynta kinetics-ka enzyme degdegga ah. Maaddaama unugyadu aanay ku xaddidnayn lifaaqyada matrixka, si degdeg ah ayaa loo diyaarin karaa oo loo isticmaali karaa imtixaannada shaqaynta iyada oo aan dib u dhac ku imanayn u hoggaansanaanta unugga. Dhaqamada ka joojinta ayaa si gaar ah faa'iido u leh marka la is barbar dhigo kala duwanaanshaha noocyada, maadaama ay ogolaadaan baaritaanno degdeg ah oo la jaanqaadaya oo dhan Ka joojinta hepatocytes ee bini'aadamka, kuwa aan -

Xasilooni dheef-shiid kiimikaad iyo Hepatotoxicity

xasiloonida dheef-shiid kiimikaadkaMarka la eego macnaha cilmi-baarista hepatocyte waxaa loola jeedaa awoodda molecule, inta badan musharraxa daroogada, si ay uga hortagto isbeddelka biochemical ee enzymes beerka. Baarista xasiloonida dheef-shiid kiimikaadka ee hepatocytes waxay u ogolaataa cilmi-baarayaasha inay saadaaliyaan nuska - nolosha iyo wax soo saarka burburin kara ee walxahan, kuwaas oo muhiim u ah horumarinta daroogada. Qaabka dheef-shiid kiimikaadka isku-dhafka ah wuxuu go'aamin karaa ma aha oo kaliya waxtarkiisa laakiin sidoo kale badbaadadiisa, maaddaama dheef-shiid kiimikaadku mararka qaarkood muujin karaan saameyn sun ah oo aan lagu arkin xarunta waalidka.

HepatotoxicityDhanka kale, waxay koobeysaa waxyeelada ay walxaha kiimikadu ku leeyihiin unugyada beerka. Isticmaalka hepatocytes ee aasaasiga ah iyo kuwa dhaqameed labadaba daraasadaha sunta waxay ka caawisaa in la caddeeyo hababka u horseedaya dhaawaca beerka. Tani waa muhiim sababtoo ah beerka, oo ah xubinta dhexe ee dheef-shiid kiimikaadka, ayaa si aad ah ugu nugul cayda sunta ah ee kiimikada deegaanka iyo wakiilada daawooyinka labadaba. Daraasadaha ka faa'iidaysiga unugyadan waxay ogaan karaan qaababka dhaawaca unugyada ama cilladda, bixinta fikrado ku saabsan dhacdooyinka hore ee dhaawaca beerka iyo caawinta saadaalinta natiijooyinka xun ee goobta bukaan-socodka.

Soo saarista enzyme waa dhinac kale oo muhiim ah oo ku xidhan shaqada hepatocyte, iyada oo la tixraacayo habka ay walxaha qaarkood u kordhiyaan isku-darka daroogada-metabolizing enzymes. Dhacdadan ayaa si gaar ah muhiim u ah maadaama ay keeni karto dheef-shiid kiimikaad oo kordhay - dawooyinka la wada maamulo, taasoo suurtogal ah inay hoos u dhigto waxtarkooda ama kordhinta wax soo saarka dheef-shiid kiimikaadka waxyeelada leh. Cilmi-baarista iyadoo la adeegsanayo hepatocytes-ka la taaban karo ayaa inta badan loogu talagalay in lagu baaro waddooyinka sharciyeynta ee xukuma soo-gelinta enzyme, taas oo iftiiminaysa isdhexgalka adag ee u dhexeeya xenobiotics kala duwan iyo awoodda dheef-shiid kiimikaadka beerka.

Bixinta iyo Xeeladaha Bartilmaameedka Hepatic siRNA

Horumarkii u dambeeyay ee faragelinta RNA (RNAi) daweynta ayaa soo bandhigtay xeelado cusub oo loogu talagalaygaarsiinta beerka la beegsanayoiyadoo la isticmaalayo RNA-yo yaryar oo faragelinaya (siRNAs). Habka muhiimka ah wuxuu ku lug leeyahay isku-xidhka molecules siRNA ee N-acetylgalactosamine (GalNAc), kaas oo fududeeya qaadashada xulashada hepatocytes iyada oo loo marayo soo-dhoweynta asialoglycoprotein (ASGPR). ASGPR waxay si aad ah ugu muujisaa dusha sare ee hepatocytes waxayna ka ciyaaraan doorka dhexe ee gudaha endocyticGalNAc-siRNAconjugates, taasoo ka dhigaysa waddo muhiim u ah beerka- gaarsiinta daroogada gaarka ah.

Cilmi-baarisyada in vitro caadi ahaan waa la shaqeeyaaGudbinta Hepatocyte siRNA ee aasaasiga ahfarsamooyinka lagu qiimeeyo waxtarka iyo gaar ahaaneed eesiRNA GalNAc Hepatocyte Delivery. Hababkani waxay u oggolaanayaan cilmi-baarayaasha inay daraasad ku sameeyaan saameynta garaacista hidda-socodka ee xaalad nafsi ahaaneed iyo inay wanaajiyaan qaababka gaarsiinta ee ugu badnaan qaadashada unugyada gudaha iyo waxtarka aamusnaanta hidda.

Guud ahaan, Bixinta Hepatic Bartilmaameedka ah ee daaweynta RNA iyadoo la adeegsanayo ASGPR - dhexdhexaadinta GalNAc

Noocyada-Faahfaahinta Cagaarshowga Gaarka ah

Hepatocytes ee aadanaha

Hepatocytes aadanaha Plateable waxay lama huraan u yihiin saadaalinta dheef-shiid kiimikaad iyo sunta maandooriyaha bini'aadamka, iyagoo siinaya hawlkarnimo sare. Ku dhegganaanshaha taarikada khaaska ah waxay u oggolaanaysaa daraasadda soo-saarka enzyme-ka dheef-shiid kiimikaadka, dheef-shiid kiimikaadka I / II, iyo dhaqdhaqaaqa gaadiidka.

Qaab aan -mid la socon,Ka joojinta hepatocytes dadka si degdeg ah uga jawaabaan xenobiotics, taasoo ka dhigaysa mid ku habboon qiimaynta dheef-shiid kiimikaad degdeg ah, daraasado nadiifin ah, iyo -

Non-Hepatocytes aasaasiga ah ee aadanaha

U ekaanshaha jireed ee aadanaha ayaa sameeyaDaanyeerka Cynomolgus Hepatocytes ee la dhejin karoiyoDaanyeerka Rhesus Hepatocytes ee la dhejin karo qiimo u leh isku xirka daraasadaha hore ee natiijooyinka aadanaha. Waxaa loo isticmaalaa in lagu qiimeeyo dheef-shiid kiimikaadka daroogada, soo-saarka ensaymka, iyo noocyada - muuqaalada badbaadada gaarka ah.

Joojinta Cynomolgus Hepatocytes daayeeriyoKa joojinta Rhesus Monkey Hepatocytes awood u yeelo qiimaynta isbarbardhigga ee hawlaha dheef-shiid kiimikaadka iyo jawaabaha degdega ah, faa'iido leh marka xogta muddada gaaban loo baahdo ka hor inta aan la dheerayn

Hepatocytes ee Canine

Ugu horrayn looga faa'idaystay cilmi-baadhista caafimaadka xoolaha iyo tarjumaada,Hepatocytes eeyga la dhejin karoiyoHepatocytes Beagle Plateablemimic in vivo physiology beerka si loo barto daroogada - dhaawaca beerka ee sababay iyo dheef-shiid kiimikaadka daawooyinka xoolaha

Kuwani waxay bixiyaan daraasado dheef-shiid kiimikaad oo degdeg ah waxaana lagu shaqaaleysiiyay imtixaannada baadhista marxaladda hore, kuwaas oo ka faa'iidaysanaya isbeddelka degdegga ah ee qaabka Hakinta.

Sprague-Dawley Rat Hepatocytes

KuwaasSprague Plateable - Dawley Rat Hepatocyteswaa ka go'doonsan Sprague-Dowley jiirka waxaana lagu dhaqameeyay qaab la jaan qaadi kara ama la dhegeysan karo. Habka Plateable, unugyadu waxay ku dheggan yihiin saxanka dhaqanka, taas oo u oggolaanaysa inay sameeyaan is-dhexgalka unugyadu deggan yihiin oo ay ilaaliyaan beerka-shaqo gaar ah muddo dheer. Habkani wuxuu si gaar ah ugu habboon yahay barashada hababka dheef-shiid kiimikaadka muddada dheer, soo-saarka enzyme, iyo qiimeynta sunta sunta ah ee daba-dheeraada iyadoo la adeegsanayo Sprague-Dawley unugyada beerka.

Marka lagu hayo xaalad aan -Joojinta Sprague-Hepatocytes ee jiirka Dawleywaxa ugu horrayn loo isticmaalaa tijaabo -gaaban. Qaabka Hakintu waxa uu fududeeyaa qiimaynaha degdega ah, sida daraasaadka dheef-shiid kiimikaadka daroogada degdega ah iyo qiimaynta kinetics enzyme, halkaas oo jawaabaha degdega ah looga baahan yahay. Habkani waa mid faa'iido leh marka la barbardhigo jawaabaha dheef-shiid kiimikaad ee u dhexeeya noocyada ama xaaladaha kala duwan.

ICR/CD-1 Jiirka Hepatocytes

Ka go'doon ICR/CD-1 jiir, kuwan La dhejin karo ICR/CD-1 Jiirka Hepatocytesu hoggaansamaan saxanka dhaqanka, iyaga oo u oggolaanaya inay sii wadaan hawlaha muhiimka ah ee beerka muddo dheer. Cilmi-baadhayaashu waxay jecel yihiin habka Plateable ee ICR/CD-1 jiirka hepatocytes marka ay xasilloon, muddada dhaqanka dheer lagama maarmaan u ah indho-indheynta tijaabada ah.

Taas bedelkeeda, Suspension ICR/CD-1 jiirka hepatocytes ayaa la dhaqamiyey iyada oo aan loo hoggaansamin, sidaas awgeed waxay sii haysanaysaa qaab-dhismeedka qaab-dhismeedka ee ku habboon daraasadaha muddada-gaaban.Joojinta ICR/CD-1 Jiirka Hepatocyteswaxay u ogolaataa in si degdeg ah loo qiimeeyo jawaabaha dheef-shiid kiimikaadka waxayna si gaar ah faa'iido u leedahay baadhisyada horudhaca ah ama marka la rabo - Isticmaalka hepatocytes-ka-joojinta ee ICR/CD-1 jiirarka waxay gacan ka geysataa in si degdeg ah loo dhiso astaamaha dheef-shiid kiimikaad oo la barbar dhigo noocyada kale ama xaaladaha tijaabada ee kala duwan.

Hepatocytes ee Feline

Qaabka la daabici karo ayaa si gaar ah faa'iido u leh daraasado dheer Daraasado diiradda lagu saaray cudurrada beerka ee feline, daroogadaHepatocytes bisadaha la dhejin karobixiyaan nooc adag. U hoggaansanaantoodu waxay sidoo kale kor u qaadaysaa dib-u-soo-kabashada morphological iyo meelaha ugu dambeeya ee shaqeynaya, taas oo ka dhigaysa moodal la doorbido ee farmashiyaha xoolaha iyo cilmi-baarista cagaarshowga.

Qaabka Joojinta wuxuu fududeeyaa cabbiraadda jawaabaha gacanta ee degdega ah ee xenobiotics, halkaas oo ku-xidhnaan la'aanta ay yarayso daahitaanka jawaabta lagu arkay dhaqamada muddada dheer.Joojinta Cagaarshowga Cagaarshowga Cat Sidaa darteed waxay muhiim u yihiin in la aqoonsado isbeddellada biochemical ee hore iyo falcelinta xun ka dib soo-gaadhista xeryahooda cusub.

Hepatocytes digaagga

Sida wakiillada moodooyinka avian-ka,Hepatocytes Digaagga la dhejin karowaxaa loo isticmaalaa daraasado isbarbardhig ah si loo fahmo kala duwanaanshaha horumarka ee shaqada beerka, gaar ahaan qiimeynta carqaladaha endocrine.

Joojinta Hepatocytes Digaaggawaxay sahlaysa in si degdeg ah, degdeg ah - daraasado weji ah oo ku saabsan dheef-shiid kiimikaadka beerka ee shimbiraha waxaana si toos ah loo barbar dhigi karaa dhiggooda naasleyda.

Noocyada Kale

Noocyada kale, Hepatocytes Minipig ee la dhigi karo, Joojinta Hepatocytes Minipig, Hepatocytes ee bakaylaha cad ee New Zealand, Joojinta Hepatocytes ee Bakaylaha Cad ee New Zealand, Joojinta Cagaarshowga Hepatocytes ee Rat Wistar, Joojinta Hepatocytes Dhammaan sidoo kale waa tusaalayaal caan ah oo loogu talagalay saadaalinta iyo sharraxaadda daroogada - isdhexgalka daroogada iyo barashada cytotoxicity daroogada.

Gabagabo

Hepatocytes waxay door muhiim ah ka ciyaaraan ilaalinta shaqada beerka iyada oo loo marayo dheef-shiid kiimikaad, sun-saarid, wax-soo-saarka bile, iyo isku-darka borotiinka. Maqaalku wuxuu hoosta ka xariiqay farqiga u dhexeeya hepatocytes aasaasiga ah iyo foomamkooda dhaqameed-la dhejin karo iyo hepatocytes-ka-joojin-mid kasta oo loo habeeyay ujeedooyin tijaabo ah oo kala duwan. Hepatocytes ee la daabici karo, oo u hoggaansanaantooda iyo sii jiritaankooda, ayaa muhiim u ah barashada saameynta dabadheeraad ah, soo-saarka enzyme, iyo hababka dheef-shiid kiimikaadka muddada dheer, halka hepatocytes-ka joojinta ay bixiyaan xaalado tijaabo ah oo degdeg ah oo isku mid ah oo loogu talagalay baaritaannada degdega ah. Intaa waxaa dheer, falanqayntu waxay ku fidsan tahay noocyada - codsiyo gaar ah, oo ka tarjumaysa sida noocyada kala duwan ee hepatocyte-ka bini'aadamka iyo hababka xayawaanka-caawinta saadaasha dheef-shiid kiimikaadka daroogada, qiimeynta cagaarshowga, iyo naqshadeynta daawaynta la beegsanayo sida RNA - waxqabadyo ku salaysan iyadoo la isticmaalayo GalNAc conjugation. Dulmarkan dhamaystiran wuxuu muujinayaa doorka muhiimka ah ee hepatocytes ee cilmi-baarista kiliinikada iyo horumarinta dawooyinka labadaba, siinta fikrado muhiim ah oo ku saabsan physiology beerka iyo hababka hoos yimaada badbaadada iyo waxtarka daroogada.