Screening of Endocrine Disrupting Chemicals using Stem Cells


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GRF 2nd One Health Summit 2013: Presentation by KANG, Dr. Kyung-Sun, Seoul National University

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Screening of Endocrine Disrupting Chemicals using Stem Cells

  1. 1. 2nd GRF One Health Summit 2013 Screening of Endocrine Disrupting Chemicals using Stem Cells Prof. Kyung-Sun Kang, DVM, Ph.D Adult Stem Cell Research Center Seoul National University, Korea 1
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  5. 5. Stem Cells prenatal postnatal Embryonic stem cells Fertilized egg ICM Fetal stem cells Blastocyst Adult stem cells 골 수 지 방 “The youngest, most primitive MSCs” Source: ’Journal of Cellular Biochemistry’, 112: 1206-1218 (2011) 5
  6. 6. New tools for drug screening : Accelerating the drug discovery Animal testing Save time ● Non-animal methods usually take less time to complete Stem cell based drug testing Low cost ● Stem cell based test offer a lower cost alternative to expensive animal test High efficiency ● Provides information related directly to humans
  7. 7. Model using Cancer Stem Cells
  8. 8. 3D Spheroid colony formation assay using human breast cancer ; enrichment of cancer stem cells Mammosphere control put a Tox tive a Human breast cancer ican nti-c a ts i stem cells on agarose coating nclu ncer d plate d in r g ED ug, Sc References •gene expression of BRCA1, BRCA2 and Her2 •evaluation of Mammosphere  Yang SR, Rahman I, Trosko JE, Kang KS. Oxidative stress-induced biomarkers for stem cell-based chemical screening. Prev Med. 2012 May;54 Suppl:S42-9. Sun et al., Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model Cytotherapy 2009, 11(3):289-298. Park et al., Gene expression analysis in SV40-immortalized human breast luminal epithelial cells with stem cell characteristics using a cDNA microarray Int J Oncol 2004, 24(6):1545-1548.
  9. 9. Regulation of MCF-7 mammosphere formation by breast cancer promoters and metformin
  10. 10. -ScienceDaily, Nov.23, 2011 -MEBO, Dec.8, 2011 -ATGCchecker, Nov, 2011
  11. 11. Induced Pluripotent Stem Cells (iPSc)
  12. 12. RESEARCH ARTICLE STEM CELLS Drug Screening for ALS Using Patient-Specific Induced Pluripotent Stem Cells Naohiro Egawa,1,2* Shiho Kitaoka,1,2* Kayoko Tsukita,1,2 Motoko Naitoh,3 Kazutoshi Takahashi,1 Takuya Yamamoto,1,4 Fumihiko Adachi,1 Takayuki Kondo,1,5 Keisuke Okita,1 Isao Asaka,1 Takashi Aoi,1 Akira Watanabe,1,4 Yasuhiro Yamada,1,4 Asuka Morizane,1,6 Jun Takahashi,1,6 Takashi Ayaki,5 Hidefumi Ito,5 Katsuhiro Yoshikawa,3 Satoko Yamawaki,3 Shigehiko Suzuki,3 Dai Watanabe,7 Hiroyuki Hioki,8 Takeshi Kaneko,8 Kouki Makioka,9 Koichi Okamoto,9 Hiroshi Takuma,10 Akira Tamaoka,10 Kazuko Hasegawa,11 Takashi Nonaka,12 Masato Hasegawa,12 Akihiro Kawata,13 Minoru Yoshida,14 Tatsutoshi Nakahata,1 Ryosuke Takahashi,5 Maria C. N. Marchetto,15 Fred H. Gage,15 Shinya Yamanaka,1,4,16 Haruhisa Inoue1,2,16† Exp Mol Med. 2012 March 31; 44(3): 202–213. Published online 2011 December 19. doi: 10.3858/emm.2012.44.3.015 PMCID: PMC3317484 Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery Jiho Jang,1,* Jeong-Eun Yoo,1,* Jeong-Ah Lee,1,* Dongjin R. Lee,1 Ji Young Kim,1 Yong Jun Huh,1 Dae-Sung Kim,1 Chul-Yong Park,1 Dong-Youn Hwang,2 Han-Soo Kim,3 Hoon-Chul Kang,4 and Dong-Wook Kim1 12
  13. 13. Direct reprogramming of human dermal fibroblasts to induced neural stem cells. NTF 1 Transfection NTF 2 Transfection Neuron Fibroblast s 7 days Astrocytes iNSC s Oligodendrocytes hMSCs - Yu et al. Manuscript in preparation 13
  14. 14. H9-NSCs hDF-iNSCs 14
  15. 15. To date, stem cells have been considered to be used for (a) basic mechanistic understanding how stem cells regulates the total genome and its cell behavior ( cell proliferation in a symmetrical or asymmetical fashion; differentiation; apoptosis, immortality, senescence, etc.); (b) regenerative medicine or stem cell therapy; (c) drug discovery; blocking EDCs (d) toxicity testing of pharmaceuticals, environmental toxicants including EDCs (e) genetic therapy (f) the role of stem cells in stem cell-derived diseases and in the aging process. (g) mimicking human tissue or organ substitute to animal experiments
  16. 16. Stem Cells, Bacteria and Inflammatory Bowel Disease Kim HS, Kang KS et. al., Gastroenterology, 2013 16
  17. 17. EDCs is an good example for the one health approach • EDCs are ; • 1) lipophilic man-made chemicals • 2) mimicking hormone-like action such as estrogen, androgens • 3) bioaccumulated in environment, animals and human through the food chains. • 4) Therefore, EDCs issue can be approached by One health concepts. 17
  18. 18. Clean our environment Improved our quality of life Go back to nature Thank you for your kind attention!