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Phoocytes ea mantlha: sesebelisoa sa bohlokoa sa ho hlapanya ho se kopane

Phoocytes ea mantlha: sesebelisoa sa bohlokoa sa ho hlapanya ho se kopane

Liver, joalo ka setho sa mantlha sa ho se sebelisoe lithethefatsi, se bapala karolo ea bohlokoa ho metabolism ea lithethefatsi le lits'ebetso tsa nrifi. Li-futatocytes tsa mantlha li na le likarolo tse felletseng tsa litšobotsi le li-enzchros tse kang cytocrolic, tse kopaneng - Ka lebaka lena, mabotho a mathomo a itlhatsoa a mangata e le molao oa mantlha oa ho theha litsebi tsa vitro, 'me a ratoa haholo metabolism ea lithethefatsi, metabolism ea lithethefatsi le likhakanyo tsa lithethefatsi le lithuto tsa lithethefatsi. Sengoliloeng sena se fana ka kakaretso ea mefuta ea 2D le ea 3D e thehiloeng ho li-Hepatocytes tsa mantlha le likopo tsa tsona ho ntlafatso ea lithethefatsi.

Mantsoe a bohlokoa: Tsona ea mantlha, Temo ea Phutheho, Temo ea 3, Metsoako, Co - Tloaelo.

Sehlopha Mefuta ea
Li-hepatocytes tse hlakileng Motho,Monkey (cynomolgus),Monkey (RHEUSUS),Ntja (Begle),Rat (Sprague - Dawley), Mouse (ICR / CD - 1), Mouse (C57Bl / 6), Feline, Minipig (Bama),Rabbit (New Zealand White).
Libaka tsa ho emisoa Motho,Monkey (cynomolgus),Monkey (RHEUSUS),Ntja (Begle),Rat (Sprague - Dawley), Rat (wistar han),Mouse (ICR / CD - 1), Mouse (C57Bl / 6), Feline,Minipig (Bama), Rabbit (New Zealand White),Hamster (LVG),Kuler Kuku.
CO - Sistimi ea setso Human, Monkey (Cynomolgus), Ntja (Beagle), Rat (SPRAUGUE - DaWley), Mouse (Mouse (CD - 1).
Lihlahisoa tse thusang Hepatocyte ea motho oa motho, Phoofolo ea liphoofolo hepatocyte thaw budoum, Hepatocyte incubation, Hepatocyte medium, Mohlahisi ea Tlhokomela, Poleiti ea Collate e kopaneng,Liliba tse 96, Liliba tse 48Liliba tse 24, Liliba tse 12, Wells, ultra - sebaka se tlase sa sehokelo sa sehokelo.

  1. 1. Ho itšehla thajana tsa Hepatocytes

Ho itšehla thajana ke mohato oa bohlokoa oa ho theha mefuta ea vitro Selde, 'me - Mohato oa Rotlen oa ho Rola ka mokhoa o tloaelehileng. Liphoole tse nyane, li-porfice tse nyane li ka etsoa ka veine ea Portal kapa tse tlase haholo tsa Vena Lintlha tse 'maloa tsa bohlokoa li susumetsa ho itšehla thajana ea thabo: pele, rantinese e lokela ho ba e sa ngolisoeng. Ea bobeli, nako ea lijo ke ea bohlokoa-Ka bobeli ba - Taba ea boraro, boemo ba sebete bo tlameha ho ba bo phethahetseng, kaha li-hepatocytes li tsotella tšenyo ea lefutso. Sebed bakeng sa ho itokisa ha lefu la eona ho lokela ho futhumatsoa ka potlako ho fokotsa litefiso tsa metabolic le ho thibela litheko tsa metabolic le ho thibela metabolic hypoxia le tse latelang tsa Ischemia.

Melao ea Hupatocytes ea Primto e sebelisitsoeng lipatlisisong tsa lithethefatsi e tjena:

1.Ta qala Qalo, ho netefatsa katleho e lokela ho ba> 80%, le nakong ea liteko, ts'ebetso ea ho fokotseha ke <20%.
2.To Liapatocytes li lokela ho khona ho ba metabolize 2 - 3 tse tsebahalang tse halikiloeng tse nang le liphetho tse tlalehiloeng ho tse tlalehiloeng ka har'a lingoliloeng.
3.Ne liteko tsa boikhathollo, likotlo tse tloaelehileng tse kang rifampicin li lokela ho eketsa tšebetso ea enzymes (e.g3
4.In Metabolism le lithuto tsa liparanta, kamora 4 - lihora tse 6 tsa li-hipatocytes tsa ho lla, sekhahla sa sehokelo se lokela ho> 70%.

  1. 2. PUSO EA PUSO QUPOCTTE 2D TEA

Moetso oa ho emisoa

E na le sethethefatsi se felletseng - e kopanyang selekane le li-cofuctors, li etsa hore e loketse ho ithuta mekhoa e mengata ea li-metabolic. Leha ho le joalo, ho na le bonnete ba botsitso ba ho emisoa likotlo tsa ho emisoa le tšebetso ea metabola butle butle joalo ka nako ea vitro ea phaello e eketsang lihora tse 4 ho isa ho lihora tse 4. Mohlala ona o sebelisoa hangata ho hakanya phetisetso ea lithethefatsi ka litekanyetso tse phahameng tsa tumello. Ha sekhahla sa tokiso se ka tlase ho 20%, boleng bo nepahetseng bo botle bo ke ke ba khethoa. Litšila tsa setso tsa ho emisoa - E thehiloe mefuta ea vitra Metabolism ea vitrolli Mokhoa oa ho emisoa ho emisoa ho hohola

Kopo:Ketsahalo ea Enzyme le Metabolic

Setšoantšo sa 1. Ho emisoa ho honotha

Mohloli: Li-motab tsa lithethefatsi, 2012,40 (9): 1860-1865

Mofuta oa hepatocytes ea Hepatocytes

Makhethe tsa mantlha li lengoa tsamaisong ea 2D ho ea kolecheng ea moetlo oa khale. Li-Ipatocytes li bontša morpholo ea epithelial, e nang le kouche e matla, hangata e hlahisa sebopeho se builoeng. Barekisi ba Npatocyte bany hepatocyte Monolayer ba kenyelletsa: 1. Ho fetoloa ha polasetiki ea sele le tšebetso.2. Ho haella ha mefuta e meng e nepahetseng ea selefono (i.e., eseng - lisele tsa parenymal) tse hlokahalang bakeng sa ts'ebetso e tloaelehileng.3. Ho sitoa ho fana ka limatlafatsi tse lekaneng le lintlha tsa parararine ho ts'ehetsa li-hepatocytes ho etsa mesebetsi ea bona (joalo ka Bile Acid lerum Protein

Likopo:

1). Tlhahlobo ea lithethefatsi - Litšebeletso tsa lithethefatsi:Sena se kenyelletsa boikemelo ba enzyme, thibelo ea enzyme le lithuto tsa liparanta. Pele, ha lithethefatsi li sebetsa e le setsebi sa phapanyetsano, se ka etsa hore seqo ke ho eketsehileng, se ka etsa hore seqosong e eketsehileng ea lithethefatsi - metabosong le likhatiso. Bohloko bo matla bo ka hlahisa mefuta e mengata ea Manyolo ka nako e le ngoe hantle, joalo ka pokello ea li-chenobarbital, cyp3C9, ugg2C9, ugg2C9, ugg29, ugg2C9, ugg29, ugg2C9, ugg29, ugg2C9, ugg2C9. Taba ea bobeli, ho na le lintho tsa bohlokoa - Mohlala, Rifampicin ke sethala se sebetsang bakeng sa IPatocytes ea motho le rabbit. Qetellong, ho na le letsoalo le phahameng la mapolanka a hlakileng a magrame a nang le leqheka le fokotsoeng ke ho fokotsoa ka tlase ho P450s le likarabo tse ngata tsa boikhathollo. Joalokaha ho bontšitsoe setšoantšong sa 3, li-Hestatocytes tsa makhopho a tlase li bonts'a tšebetso e tlase ea basal ea cyp1a2, cyp2b6, le cyp3a4. Ka hona, li-Hepatocytes tse phetseng hantle tsa litoro tse loketseng tsa poleiti li hlokahala ho fumana data e loketseng ea 'mele.

 

Setšoantšo sa 2. Kamano pakeng tsa ho beha letsoalo la ho lla ha li-hepatocytes tsa batho ba llelang le ho inehela

Mohloli: Technoloji ea Sekoahelo sa Lithethefatsi, 2010, 7: 188 -

2). Tlhahlobo ea Hepatotoxicity: Ho shebella lintho tsa mordopolo tsa microscope, joalo ka morfology ea seleforlogy, le lipid dropplet Ho lemoha necrocyte necrosis (joalo ka ha ho bonts'itsoe ke Asparte Aminotransfese, le Angon Aminitrantrase) le Apoptoration (dna phaello). Bakeng sa cytokine - "Cytotoxixicity e ngotsoeng ka potoloho, litso tse le 'ngoe tsa li-monolaymaer tsa li-hepatocymal li ke ke tsa bolela likarabo tse fapaneng ka lebaka la molao, lisele tsa lisepareba le lisele tsa lisediraja.

3). "Mokhoa o phetoang" bakeng sa ho ithuta ho liehang ho soma butle le metabokolites ea eonaKetsahalo ea lithethefatsi - metabolising e ntle ka li-apatocytes e qala ho fokotseha kamora lihora tse 24. Kamora ho fepa li-apatocytes tse poteletseng ka serum -


Setšoantšo sa 3. Hepatocyte RAPATocyte ea Phello ea Metholo

Mohloli: Litlhaku tsa lithethefatsi tsa Metabolism, 2016, 10: 3 - 15

3). Lekola mokhoa oa ho phalla oa cellular, mamello, ho baleha ka mamello, le ho se nka lithethefatsi tsa tšepe tsa Hepatocyte - O ne a fana ka litlhare tse nyane tsa nyutlei ea nyutlei.

Mohlala oa Leseli la Sandwich

VITRO, Tpatocytes e ka bakoa pakeng tsa likarolo tse peli tsa Molekane kapa moeti oa ho ea le meaho ea VIVO, e tsejoang ka hore ke moferefere oa sandwich. Tsoekono e ile ea ikakhetse pakeng tsa likhechana tse peli - Ntle le moo, litsong tsa bo-sandwich li ka khutlisetsa phepelo, li lumella serapa se nepahetseng sa bastolaral le cantalicolar hammoho le sebopeho sa ts'ebetso ea Sechaba, hammoho le sebopeho sa ts'ebetso ea Setefane, hammoho le sebopeho sa tšebetso ea 2).



Setšoantšo sa 4. Secction ea li-greaterer in the Hepatocyte Sandwich mohlala

Mohloli: Technoloji ea Sekoahelo sa Sekoahelo sa Sekoahelo sa Sekoahelo sa Lithethefatsi, 2010, 7, 188 -

Likopo:

  1. 1). Ho lekanya lintho tse ngata tsa biliary tsa metsoako.
  2. 2). Ho lekola ho tsamaisoa ha metsoako ea mamello le ea Exogenus le metabotonates.
  3. 3). Ho lekanya ka bolokolohi ba metaolism le lipalangoang, le ho aha ligerthogy - mefuta e thehiloeng ea mananeo.
  4. 4). Ho ithuta Hepatoaxicity le ho fana ka mefuta ea lithethefatsi bakeng sa lithethefatsi tsa clinical - Ho lemala hampe. Lintlha li kopantsoe ka mefuta ea litsamaiso tsa pharmacology ho bolela lithethefatsi - Ho lemala ho batho ba khathollang ho batho.
  5.  
    1. 3. PUSO EA PUSO EA DEPETAYTE 3D
  6. Ka sistimi ea setso ea 3D, mattrictes e ea moetlo ho tse tharo - Boxics ea boholo ba merafong e bapisoang le litso tsa meralo ea VIVO. Litsamaiso tsena li khothaletsa Cle, sele ea Therix, ho ka khutlisetsa likokoana-hloko tse ling tsa Merishene, e ka khutlisang metabolism ea lipalesa tsa sebete, liphiri tsa protheine le ho itlhahlotsoa. Mefuta ea mantlha ea Hupatocyte 3d e ka sebelisoa ho ithuta sebete - Mesebetsi e tobileng ho vivo - Mesebetsi ea Bomoko.

    Mohlala oa Sphiroid

Ka mekhoa e kang Ultra - Setso se tlase sa sehokelo, le setso sa masene Monyetla o mong oa setso sa mafu a spheroid ke hore e mong le e mong a e-spherife e hloka lisele tse 1,330 - Liphuputso tsa morao-rao li bontšitse hore litso tsa mantlha tsa Ipatocyte li ka tšehetsa ho fihlela ho senyeha lithethefatsi, li-enzyme tsa pompo, litšoantšiso, litšoantšiso, litšoantšiso, litšoantšiso, litšoantšiso, li-enzyme tse setseng ka matsatsi a 14. Leha ho le joalo, sebete se rarahane haholo ho feta seleng e ngata. Ka lehlakoreng la lishool la lishoolteral a sebelisana le mali, ha ho ntse ho tloha ka lehlakoreng le leng, leo e leng karolo ea bohlokoa ea sebete, 'me sena se se ke sa phetoa mohlala oa speroid.

Likopo:

  1. 1). Ho ithuta ha likhama tse halikiloeng butle butle ka tumello ea thepa le metabosotes eona.
  2. 2). Lipatlisiso tsa hepato.
  3. 3). Tlhatlhobo ea ho phahamisoa ha andocytosis, ho phonyoha ho baleha, le litlamorao tsa ho nka lithethefatsi tsa lefutso tsa lefutso.


Setšoantšo sa 5. Mokhoa oa setso oa Speheroid

Liver Ominsovoids

Tlhaloso ea khoebo ke: Meaho ea 3D e nkiloeng ho lisele tsa spem, lisele tsa projene, li ka etsisa mesebetsi ea Vivo, e ka e kopanyang ea vivo - ho ngolla li-vior tsa vivo. Li-li-Orvonood li khetholloa e le mohlala o tsoetseng pele haholo bakeng sa lipatlisiso tsa thuto ea bophelo ba batho ba birigy.

Mehloli ea sele bakeng sa kaho ea metsoi ea litsie:

Lisele tsa Putripopont Stem (PScs):

Lisele tsa Mokoetlisi tsa ENCRYOL (ESCS) le lisele tse isitsoeng lisele tsa motlakase (IPSC Tlas'a tšusumetso ea lintlha tse khethehileng tsa matšoao a matsoho, li khetholla ho lefutso - joalo ka lisele tsa tšebetso le tšebetsong. Leha ho le joalo, sebete se tsoa ho PScs se ka felisoa ke litheolelo tsa naha le tsa lefutso, ho bontša liphetoho tsa chrosomal nakong ea ho qala.

Likopo:

  1. 1). Mefuta ea lefu la li-pitsa
  2. 2). Mefuta e nang le lefu la mashano
  3. 3). Ho hlahloba lithethefatsi tsa cytostorics
4). Ho fetisoa le lefu la maloetse

Lisele tsa sebete - lisele tse tsoang: Tsena li kenyelletsa li-chonganiocytes le li-hepatocytes. Li-Hepatocytes tse holileng holima li-silet tsa celm le bokhoni ba ho atisa ho tsepamisa maikutlo maemong a itseng. Ho bapisoa le PSC - Metsoako e metshong, ho tsoa li-granome tse kholo ho tsoa ho lisele tsa mantlha, tse nang le mokhoa o tsitsitseng oa phenoti le lefutsong. Leha ho le joalo, ho na le bolelele ba nako e telele - Metsoako ea bophelo ba hepaotoction ea batho ba holileng holima e na le li-Hepatocytes tsa ho fetisoa ha li-actatocy. Metsoako ea batho ba baholo ba holileng hepatocyte e lula e le thata.

Mokhoa oa setso (Setšoantšo sa 6): Lisele tsa sebete li tšeloa ho ba le lisele tse le 'ngoe tsa sebete,' me lisele li entsoe ka 24 - poleiti ea boqhetseke. Incubbate ka selibeng sa sele inter inbator (37 ° C Kamora ho tiisa, eketsa moetlo o khethehileng oa setso. Temana kamora nako e ka bang matsatsi a 14. Pheta bo-ramahlauli ba mantlha ka phapang kamora 7 - Matsatsi a 10.

Likopo:

  1. 1). Mefuta ea Hepatotoxicity
  2. 2). Ho vitra matabolism ea vitrolm ea vitrol
  3. 3). Eseng - Lefu la joala la mafura
  4. 4). Ntlafatso ea lithethefatsi bakeng sa Bekiness le maloetse a sebete a sebete

Setšoantšo sa 6. Setso le ts'ebetso ea temana ea lisele - OR'CIOID ea Liver

Mohloli: sele le Bioscience (2023) 13: 197

Papiso ea setso sa spheroid le setso sa khale

TLHOKOMELA

Spheroid

Ho buisanoa

Mofuta oa sele

Hepatocytes

Lisele tsa Steme, lisele tsa progentor, ho kula lefu la ho holisa bophelo bo holileng

Mochine

E sebelisa tloaelo ea tlhaho ea lisele tse hōlileng ho kenya karohano ho boloka phapang

E nchafatsa nts'etsopele ea e-tlose kapa e nchafatso ea lisele

Mokhoa oa setso

Mekhoa e Thibela Khoebo ea Lie

Gel ea matrix

Setso sa Sebetsa

Maemo a tloaelehileng ntle le litlatsetso tse ikhethang

E tlatselletsoa ka litheolelo tsa mefuta ea ho fapana le tsa bohlokoa le lintho tse kholo

Khetholo ea sele

Lisele li lula maemong a arohaneng

Qalo ea pele e tlase, ka tekanyo e itseng ea tloaelo e fumanoang

Nako ea setso

Libeke tsa ≤5

Likhoeli tsa ≤11


4. Primitom Hepatocyte Co - Mohlala oa Setso

    1. 2D hepatocyte co - mohlala oa setso

      Ho 2D Heat Heat Nakhon Depatocyte Co - Mohlala oa setso, ho tsoaloa mefuta ea li-coes tse peli, 'me ha li kopantsoe' me li lekiloe sebakeng se le babeli - Bokaholimo ba Metona. Karolo ea bohlokoa ea mohlala ona ke tšebelisano e tobileng lipakeng tsa mefuta e fapaneng ea mefuta e fapaneng, tšebelisano lipakeng ka li-cytokines le likhamphani tsa lik'hemik'hale le lipuisano tsa lik'hemik'hale. Mesebetsi ea Hupacyte ea Hupatocyte, e kang tlhahiso ea albabin le bokhoni ba metabolis, e ka bolokoa libeke tse tharo.

      Likopo:

      1. 1). CO ea mantlha ea Hepatocytes CO - e lenngoeng ka fibroblast: mohlala ona o sebelisoa bakeng sa ho ithuta ka ho hlaka - metsela ea metsoako le metabolaite ea bona.
      2. 2). Lisele tsa mantlha tsa Ppatocytes CO - lisele tse sa tloaelehang tsa bo-parentymal, le lisele tsa li-andowhinines), ha li ntse li thusa bashente ka mor'a ho pepesetsoa lingaka ka lebaka la ho pepesetsoa lithethefatsi.
      3. 3). COST DITOYTES CO COS - Senoko sa T se sentsoe: Moetsi enoa o sebelisoa ho bona li-metabolism tsa lithethefatsi -
      4. 4). Hepatomax ™CO - Tsamaiso ea Mefuta: Iphase e bile le CO - Sistimi ea Mefuta e Tsoang Mechabeng e fapaneng, e tsejoang e le Hepatomax. Ka CO - Batho ba lemang linko tsa mantlha tsa batho ba nang le lisepa tsa stemal, ho ka etsahala hore ba boloke lithethefatsi tse ntle - Sistimi ena e loketse ho ithuta butle - metaboration "

      Lenane lena la setso le fana ka sethala se amehang haholoanyane bakeng sa ho lekola metabolism, chefo - Mefuta ea Metso e fapaneng e kenya letsoho mosebetsing oa litsotsi le lefu.

      3D hepatocyte co - mohlala oa setso

      Tsamaisa 3D CO - Tloaelo: Mokha ona o kenyelletsa ho kopanya mefuta e 'meli kapa ho feta ea lisele tsa sebete (e.G: Lisele tsa mantlha tsa moea Tsamaisa ka kotloloho 3D Co - Tloaelo e lumella tšebelisano lipakeng tsa lisele tse fapaneng tsa sebete ho isa ho - Ho fana ka puisano lipakeng tsa li-cepsivantes.

      Likopo:

      1. 1). Liver Fibrosis Moden: o ne a tloaetse ho ithuta mekhoa le tsoelo-pele ea sebete Fibrosis ea sebete.
      2. 2). Lithethefatsi - kotsi ea li-sebete (Dili) mohlala: e thusa ho etsisa le ho hlahloba tšenyo ea sebete e bakoang ke lithethefatsi.
      3. 3). Tšebelisano ea lithethefatsi, metabolism ea lithethefatsi le ea enzyme: e lekola mokhoa o fapaneng ea lithethefatsi, le hore na li khothaletsa li-enzyme tsa sebete joang.

      IndD 3D CO - Tloaelo: Mokhoa ona o sebelisa mokhoa oa ho arohana oa 'mele oa ho arohana (e., transwell kapa lisebelisoa tse ling Puisano pakeng tsa lisele li etsahala ka li-cytokines tsa quple3.

      Likopo:
      E sebelisoang bakeng sa ho ithuta ho sa ikopanye le puisano lipakeng tsa lisele tsa sebete 'meleng.


      Ka kakaretso, Iphase, e ne e le moetapele oa ho etsa lipatlisiso tsa vitro, ho fana ka tharollo e felletseng bakeng sa ho se atlehe ho lithethefatsi. Ho tsoa ho khethollo le setso sa li-futate tsa mantlha ho tsoa ho mefuta e fapaneng ea lihlahisoa tsa ts'ebeliso ea li-vitro bakeng sa sejana sa vitro se sibolotsoeng ke moriti le nts'etsopele. Re molekane ea tšepahalang indastering ea meriana ea meriana, ikemisetseng ho fana ka sehiloeng - Litharollo tsa lipatlisiso tsa bongaka.


Nako ea poso: 2025 - 2025 - 01 - 16 14:31:28
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