Keywords:Organoid, 3D Kurima, 3D Spheroid Culture, 3D cell culture, Primary Hepatocytes, Primary human hepatocytes, Primary monkey hepatocytes, Primary dog hepatocytes, Primary rat hepatocytes, Primary mouse hepatocytes, Ultra-low attachment culture plate

IPHASE Zvigadzirwa

Nhanganyaya

Iko kukurumidza shanduko yeOrganoid uye 3D cell tsika tekinoroji iri kushandura preclinical research. Sezvo makambani emishonga anotsvaga zvakawanda zvekufungidzira mukativitro models, yechinyakare mbiri - dimensional (2D) sero tsika iri kuwedzera kutsiviwa ne physiologically yakakodzera 3D kurima masisitimu.

Chiitiko chakakosha chakauya muna Kubvumbi 2025 apo US FDA yakazivisa hurongwa hwekudzikisa zvinodiwa zvekuongororwa kwemhuka zvemonoclonal antibody kuchengetedzwa kwekuongorora panguva enco.kukurudzira kutorwa kweNew Approach Methodology (NAMs), kusanganisira organoids uye advanced human cell-based modhi. Kuchinja kwepolicy uku kunoratidza kukosha kuri kukura kwevanhu-inoenderana in vitro masisitimu ekuvandudza zvinodhaka.

Pakati peaya matekinoroji, Primary Hepatocyte 3D Spheroid Tsika yave imwe yeanonyanya kushanda uye anogamuchirwa zvakanyanya chiropa mhando. Nekubvumidza hepatocytes yekutanga kuzvidzora - kuungana kuita matatu - dimensional spheroids, vaongorori vanogona kuchengetedza chiropa-chaiwo mabasa kwenguva yakareba apo vachiwana zvakawanda zvekufungidzira data rezvinodhaka metabolism, hepatotoxicity, uye chiropa chekutsvaga chirwere.

Chii Chiropa Organoids uye Hepatocyte Spheroids?

Organoids matatu - dimensional multicellular zvimiro zvakatorwa kubva stem maseru anodzokorora akakosha ekuvaka uye anoshanda maitiro enhengo dzekuzvarwa. Chiropa organoids vakaratidza kugona kukuru mukurapa kwekuvandudza, kuenzanisa kwechirwere, uye kurapwa kwemunhu.

Kuenzaniswa ne stem cell-yakabva organoids, primary hepatocyte spheroids inomiririra yakapfava uye inoberekana zvakanyanya ye 3D spheroid tsika. Panzvimbo pekuda matrices akaoma ekuwedzera kana maprotocol ekusiyanisa, achangobva kuparadzaniswa Primary Hepatocytes anongoerekana aunganidza pasi pe ultra- low attachment mamiriro ekuumba compact multicellular spheroids uchichengetedza zvakakosha hepatic phenotypes.

Iyi nzira yakananga yakaita kuti hepatocyte spheroids ive imwe yemhando dzechiropa dzinoshandiswa zvakanyanya pakutsvakurudza kwemishonga.

Nei Tsika ye3D Inodarika Yakajairika 2D Tsika

Primary hepatocytes inokurumidza kurasikirwa yavo yakasiyana-siyana phenotype painogadzirwa seyakajairika monolayers. Mukati memazuva mashoma, chiropa-chaiwo mabasa mazhinji anodzikira zvakanyanya, anosanganisira: Cytochrome P450 enzyme activity、Albumin secretion、Bile acid metabolism、Drug transporter expression、Cellular polarity. Izvi zvinogumira zvinoderedza kukosha kwekufungidzira kwechinyakare 2D tsika dzenguva refu-yenguva chepfu zvidzidzo.

Kusiyana neizvi, 3D spheroid tsika inodzoreredza yakakosha sero - kusero kupindirana uye microenvironmental architecture inowanikwa mune yechiropa tishu. Iwo anokonzeresa spheroids anoratidza akavandudza hunhu hwemuviri kuburikidza nekuvandudzwa kwesero kutaurirana, okisijeni gradients, kupararira kwekudya, uye kuchengetedza kwehepatic polarization.

Nokudaro, primary hepatocyte spheroids inochengetedza kushanda kwechiropa kwakagadzikana kwemavhiki pane mazuva, zvichiita kuti zvive zvakakosha kune zvidzidzo zvisingaperi zvekushandisa zvinodhaka.

Zvakanakira zvePrimary Hepatocyte 3D Spheroid Tsika

1. Yakareba-Term Functional Stability

Mukana wakakosha we3D primary hepatocyte spheroid tsika ndeyekureba-kuchengetedzeka kwechiropa-chaiwo mabasa. Nekusimudzira sero rakakura - kudyidzana kwesero uye kudzoreredza imwe physiologically yakakodzera microenvironment, spheroids inochengetedza yakakosha hepatic maitiro ayo anorasika nekukurumidza mutsika dze2D. Pasi pemamiriro ezvinhu akagadziridzwa, primary hepatocyte spheroids inochengetedza kugadzirwa kwealbumin yakagadzikana, CYP450 enzyme basa, Phase I uye Phase II metabolism, uye kutaura kwemutakuri wezvinodhaka kwemazuva anopfuura 21. Uhu hurefu hwehupenyu hwekushanda hunogonesa kufungidzira mu vitro modhi yezvinodhaka metabolism, hepatotoxicity assessment, uye chisingaperi chiropa chirwere chekutsvaga.

2. Kuwedzeredzwa kwePhysiological Relevance

Imwe yemabhenefiti makuru e3D hepatocyte spheroid tsika kugona kwayo kudzoreredza zvakakosha zvechiropa microenvironment. Kuburikidza neyakakura sero - kudyidzana kwesero uye kuumbwa kwetishu - senge matatu - dimensional architecture, spheroids inomisikidza physiologically yakakodzera oxygen uye zvinovaka muviri gradients uku ichichengetedza hepatic polarity uye cellular basa. Somugumisiro, hepatocytes yekutanga inoratidzira mabasa emagetsi anonyanya kufanana neaya akaonekwa mu vivo, zvichiita kuti kuve nekuvandudzwa kwekufanotaura kwezvinodhaka metabolism, hepatic function, uye drug-induced chiropa kukuvara (DILI) zvichienzaniswa neyakajairwa 2D monolayer tsika.

3. Zvikumbiro muDrug Discovery uye Chiropa Research

Iko kuwedzeredzwa kwehutano hwehupenyu uye kwenguva refu - kugadzikana kwekushanda kwePrimary Hepatocyte spheroids vakavaita maturusi anokosha kumativi akasiyana-siyana ezvidzidzo zvekutsvakurudza kwebiomedical. Zvinoshandiswa zvakanyanya mumishonga metabolism uye zvidzidzo zve pharmacokinetic, hepatotoxicity assessment, DILI kufanotaura, CYP induction uye inhibition assays, uye metabolic stability test. Mukuwedzera, hepatocyte spheroids inopa yakasimba mu vitro mienzaniso yekuongorora zvirwere zvechiropa, kusanganisira kwete - doro steatohepatitis (NASH), chiropa fibrosis, uye viral hepatitis. Kugona kwavo kudzokorodza zvirinani chiropa physiology zvakare kunoita kuti vanyatsokodzera mushonga chaiwo, mushonga wekuvandudza, uye mamwe maapplication epamusoro ekushandura.

Kuvaka Kuvimbika 3D Hepatocyte Spheroids

Kubudirira 3D spheroid tsika zvinoenderana nezvinhu zvitatu zvakakosha:

1. High-quality Primary Hepatocytes

Hunhu hwesero hunotaridza zvakananga spheroid morphology, kugona, uye kureba - kushanda kwenguva refu.

IPHASE inopa yakakwirira-inoshanda cryopreserved primary hepatocytes kubva kumarudzi akawanda, kusanganisira:

• Primary Human Hepatocytes
• Primary Monkey Hepatocytes
• Primary Imbwa Hepatocytes
• Primary Rat Hepatocytes
• Primary Mouse Hepatocytes

Ese mahepatocyte anodzorwa nehunhu hwakasimba kuti ive nechokwadi chekubudirira kwepamusoro, kuita kunoenderana, uye batch-ku-kuberekana kwebatch.

2. Yakagadziridzwa 3D Tsika Media

Specialized midhiya yakakosha kune ese ari maviri spheroid kuumbwa uye refu-kugadziriswa kwenguva refu.

Iyo IPHASE mafambiro ekushanda inosanganisira:

• Hepatocyte Thaw Medium
• Hepatocyte 3D Spheroid Formation Medium
• Hepatocyte 3D Spheroid Maintenance Medium

Iyi midhiya inotsigira kuunganidzwa kwakanaka uku ichichengetedza kushanda kwehepatic mukati menguva yakawedzera tsika.

3. Ultra-Low Attachment Culture Plates

Kuvimbika spheroid kuumbwa kunoda tsika midziyo inodzivirira sero adhesion.

IPHASE Ultra- Yakaderera Attachment Culture Plates inogonesa hepatocytes kuti iite yega - kuungana mumayunifomu spheroids isingade extracellular matrix coatings, ichipa yakanakisa kuenderana kune yenguva dzose laboratory workflows.

Kuedzwa Kusimbiswa

Ichishandisa cynomolgus monkey primary hepatocytes, IPHASE yakabudirira kugadzika 3D chiropa spheroids mukati memazuva manomwe ichishandisa yakagadziridzwa tsika system.(Mufananidzo1&2).

Mufananidzo 1. Mumiririri 3D spheroids yakagadzirwa kubva kuIPHASE Primary Cynomolgus Monkey Hepatocytes (Roti K0125E069).

Mufananidzo 2. Mumiririri 3D spheroids yakagadzirwa kubva kuIPHASE Primary Cynomolgus Monkey Hepatocytes (Roti K0124E022).

Kuti uwedzere kusimbisa kushanda kweIPHASE 3D Primary Hepatocyte Spheroid Culture System, hepatocytes yekutanga kubva kumarudzi akawanda akagadzirwa achishandisa maitiro akafanana akaenzana, kusanganisira cynomolgus monkey (Roti K0125E086), beagle dog (Roti B0125H018), uye Sprague - Dawtesley rat hepato. Albumin secretion mutsika yepamusoro yakayerwa mushure memazuva 7 etsika ye spheroid sechiratidzo chekushanda kwechiropa chekushanda (Mufananidzo 1). Ese marudzi matatu akabudirira kuumba yakagadzikana spheroids uye yakaramba ichionekwa kugadzirwa kwealbumin, zvichiratidza kusimba uye kuberekana kweiyo IPHASE 3D tsika chikuva pamhando dzakasiyana dzemhuka.

Kuti uongorore kwenguva refu - kugadzikana kwekushanda kwema spheroids, cynomolgus monkey hepatocytes (Roti K0124E022) yakagadzirwa kwemazuva makumi maviri nerimwe. Albumin secretion yakaongororwa panguva dzakawanda dzenguva munguva yose yetsika (Mufananidzo 2). Kugadzirwa kwakasimba kwealbumin mukati menguva refu - tsika yenguva refu inoratidza kuti IPHASE 3D spheroid system inochengetedza chiropa-chaiwo mabasa, ichitsigira mashandisirwo ayo muzvidzidzo zvisingaperi zvehuchetura, zvinodhaka metabolism, uye kwenguva refu -

Mufananidzo 1. Albumin secretion ne 3D spheroids yakagadzirwa kubva kuprimary hepatocytes yemarudzi akasiyana-siyana mushure memazuva manomwe etsika.
Mufananidzo 2. Albumin secretion ne cynomolgus monkey primary hepatocyte spheroids yakagadzirwa kwemazuva manomwe uye 21.
IPHASE Yakazara Solution ye3D Chiropa Models

Kutsigira kukura kuri kudiwa kweyepamusoro 3D cell tsika uye Organoid tsvagiridzo, IPHASE inopa yakasanganiswa yekufambisa kwehepatocyte spheroid tsika, kusanganisira:

• Cryopreserved Primary Human Hepatocytes
• Primary Monkey Hepatocytes
• Primary Imbwa Hepatocytes
• Primary Rat Hepatocytes
• Primary Mouse Hepatocytes
• Hepatocyte Thaw Medium
• Hepatocyte 3D Spheroid Formation Medium
• Hepatocyte 3D Spheroid Maintenance Medium
• Ultra- Yakaderera Attachment Culture Plates

Zvigadzirwa izvi zvinogonesa vaongorori kuti vagadzire yakasimba uye inoberekana chiropa spheroid modhi yekuwana zvinodhaka, toxicology, modeli yezvirwere, uye tsvakiridzo yekushandura.

Mhedziso

Sezvo masangano ekutonga achiwedzera kukurudzira vanhu-akakodzera nzira dzekuyedza, 3D Primary Hepatocyte Spheroid Tsika iri kuita chikuva chakakosha chekutsvaga chiropa chemazuva ano.

Nekuchengetedza hepatic phenotype, kuvandudza hutano hwehupenyu, uye kutsigira zvidzidzo zvenguva refu -

Iine yakakwirira-yemhando Yekutanga Hepatocytes, yakagadziridzwa tsika midhiya, uye nyanzvi Ultra- Yakaderera Attachment Culture Plates, IPHASE inopa vaongorori mhinduro yakakwana yekuvaka inoberekana, yakakwirira-kuita 3D chiropa modhi inomhanyisa kuwanikwa kwezvinodhaka uye biomedical research.