screening of endocrine disrupting chemicals using stem cells
DESCRIPTION
GRF 2nd One Health Summit 2013: Presentation by KANG, Dr. Kyung-Sun, Seoul National UniversityTRANSCRIPT
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Screening of Endocrine Disrupting Chemicals using Stem Cells
Prof. Kyung-Sun Kang, DVM, Ph.D
Adult Stem Cell Research Center Seoul National University, Korea
2nd GRF One Health Summit 2013
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Stem Cells
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ICMBlastocystFertilized egg
Source: ’Journal of Cellular Biochemistry’, 112: 1206-1218 (2011)
“The youngest, most primitive MSCs”
postnatalprenatal
골 수 지 방
Adult stem cellsAdult stem cellsFetal stem cellsFetal stem cellsEmbryonic stem cellsEmbryonic stem cells
Animal testing Stem cell based drug testing
New tools for drug screening : Accelerating the drug discovery
● Non-animal methods usually take less time to complete
● Stem cell based test offer a lower cost alternative to expensive animal test
● Provides information related directly to humans
Save time Low costHigh
efficiency
Model using Cancer Stem Cells
3D Spheroid colony formation assay using human breast cancer ; enrichment of cancer stem cells
Human breast cancer stem cells on agarose coating
plate
putative anti-cancer drug,
Toxicants including EDSc
control
Mammosphere
•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.
References
Regulation of MCF-7 mammosphere formation by breast cancer promoters and metformin
-ScienceDaily, Nov.23, 2011
-MEBO, Dec.8, 2011 -ATGCchecker, Nov, 2011
Induced Pluripotent Stem Cells (iPSc)
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RESEARCH ARTICLESTEM CELLS
Drug Screening for ALS Using Patient-Specific Induced Pluripotent Stem CellsNaohiro 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 discoveryJiho 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
Direct reprogramming of human dermal fibroblasts to induced neural stem cells.
Fibroblasts
Oligodendrocytes
Astrocytes
Neuron
iNSCs
7 daysNTF 2
Transfection
NTF 1Transfection
hMSCs
13- Yu et al. Manuscript in preparation
H9-NSCs
hDF-iNSCs
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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
Stem Cells, Bacteria and Inflammatory Bowel Disease
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Kim HS, Kang KS et. al., Gastroenterology, 2013
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.
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Clean our environmentImproved our quality of lifeGo back to nature
Thank you for your kind attention!