ReproHepato Human iPS Cell-derived Hepatocytes 人類iPS細胞衍化之肝細胞

Reprocell
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ReproHepato image

細胞層級的高通量篩檢系統,有助於早期藥物開發階段,快速評估上千種化合物特性。然而,這樣的篩選通常依賴於高度增殖或癌變的細胞株,在正常人類細胞中不一定能準確顯示出受影響的化合物。初代細胞(primary cell)的使用相當常見,但是它們有使用的限制且批次間變異性大。

人類iPS細胞是一個有可靠的正常人類細胞的來源,因為iPS細胞具有自我更新潛能和多能性分化能力,幾乎可分化成任何類型的體細胞。ReproCELL建立了專有技術,以提供人類iPS細胞來源的肝細胞(ReproHepato),無數量限制地生產高品質、完全分化的肝細胞,使得高通量篩選僅有微小的批次變化。

ReproCELL肝細胞優點

  • 全球第一個商品化,從iPS細胞衍化出具有CYP活性的人類肝細胞
  • 對照組為初代細胞(primary cells)時,有穩定的CYP活性和誘導力(3A4/1A2/2C9/2C19)測試結果,培養中細胞壽命長
  • 細胞為已分化細胞,使用套組中的Maitenance Medium培養六天後,該細胞則可進行CYP assay試驗
  • 細胞需儲存於-80℃,液態氮可能會降低其活性
  • 帶有高活性CYP22D6P的產品已被研發生產
  • 另提供CYP assay合約式檢測服務

人類iPS細胞衍生之肝細胞 : 高純度且具有CYP活性

ReproHepato細胞帶有典型的人類肝細胞外型和特徵,表現肝細胞組織專一性蛋白,如CYP3A4、HNF4a、E-cadherin,或高比例的白蛋白(albumin) 。

ReproHepato BE

明視野影像

ReproHepato PAS

PAS 染色:顯示肝醣囤積

ReproHepato Immune

免疫染色 :
G / E-cadherin
R / HNF4a

ReproHepato FACS CYP3A4

流式細胞儀分析: CYP3A4(+)細胞

ReproHepato FACS Albumin

流式細胞儀分析:帶有白蛋白細胞

穩定的CYP和誘導力測試結果

ReproHepato CYP3A induction inhibition

如同原代肝細胞,CYP3A4的活性是通過典型的誘導劑和抑製劑以劑量效應的方式調控,其他CYP細胞色素(1A2/2C9/2C19)的活性和誘導力,被觀察到具有和原代肝細胞相同水平的反應。現在正開發中即將推出的ReproHepato版本中,還觀察到CYP2D6活性。

更穩定的實驗結果 : 批次間差異小

相較於初代肝細胞(primary hepatocytes),ReproHepato肝細胞在CYP活性和誘導力測試中,批次間差異較低,品質穩定。

ReproHepato comparison 3A4 absolute

利用冷光(luminescence)進行 基態和rifampicin誘導CYP3A4活性測試

ReproHepato comparison 3A4 ratio不同批次肝細胞CYP3A4活性變化比較

ReproCELL肝細胞

產品貨號 產品名稱 產品數量 產品分類
RCDH001N ReproHepato Human iPS Cell-derived Hepatocytes 8.25×106 cells/vial (frozen cells, for plating one whole 96-well plate)  Kit
RCDH101 ReproHepato Culture Medium Basal medium: 80 mL Supplement: 400 µL  Reagents
RCDH301 ReproHepato Assay Medium  Reagents
RCESDH401 CYP Assay Service  Reagents
  1. Inamura, Mitsuru and Yokoyama, Chikafumi. “Human iPS cell-derived hepatocytes for drug screening.” Regenerative Medicine (2013)
  2. Scott, Clay W., Matthew F. Peters, and Yvonne P. Dragan. “Human induced pluripotent stem cells and their use in drug discovery for toxicity testing.” Toxicology letters 219.1 (2013): 49-58.

Additional Publications

Presentations

  • Society for Biomolecular Sciences(SBS), 14th AnnualConference and Exhibition 2008 (St. Louis), poster session, April 2008.
  • IBC AsiaÕs 4th Annual Stem Cells Asia Congress (Singapore), oral session, June 2008.
  • ELRIG and SBS Present: Drug Discovery (UK)poster session, September 2008.
  • Advances in Stem Cell Discoveries (San Francisco) oral session, September 2008.
  • Stem Cells: Drug Discovery and Therapeutics (London) oral session, February 2008.
  • Society for Biomolecular Science 15th Annual Conference (France), poster session, Best Poster 2009 Award-winning, April 2009.
  • Stem Cells and Regenerative Medicine Europe (UK), September 2009,Best Poster 2009 Award-winning.
  • MipTec Conference 2009, October 13-15, Basel Invited Lecture.
  • The 74th Annual Scientific Meeting of the Japanese Circulation Society (Kyoto), March 2010.
  • The 130th The Pharmaceutical Society of Japan (Okayama),March 2010.
  • The Society of Toxicology (SOT) 51st Annual Meeting (CA, USA), poster session, March 2012.
  • Safety Pharmacology Society (SPS), 13th annual meeting 2013 (Rotterdam, Netherlands), poster session, September 2013.
  • Automated Patch-Clamp systems and Ion Channel Expressing Cells 2013 (Tokyo), Verbal presentation 2013 Nov.
  • The 7th Takeda Science Foundation Symposium (Osaka), Poster presentation 2014 Jan.
  • Inamura, Mitsuru and Yokoyama, Chikafumi. “Human iPS cell-derived hepatocytes for drug screening.” Regenerative Medicine (2013)
  • Scott, Clay W., Matthew F. Peters, and Yvonne P. Dragan. “Human induced pluripotent stem cells and their use in drug discovery for toxicity testing.” Toxicology letters 219.1 (2013): 49-58.