This document discusses the use of stem cells for screening endocrine disrupting chemicals (EDCs). It describes how stem cells can be used as a non-animal alternative for drug testing that is less expensive and more efficient than animal models. Specifically, it outlines research using cancer stem cells to test for anti-cancer drugs and EDCs. The document also discusses induced pluripotent stem cells and their potential for modeling human diseases for drug discovery applications and toxicity testing. Finally, it notes that stem cells provide opportunities for basic research into mechanisms of cell behavior and potential applications in regenerative medicine, genetic therapy, and studying stem cell-related diseases and aging.

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
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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)
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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. Model using Cancer Stem Cells

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. Regulation of MCF-7 mammosphere formation by breast cancer
promoters and metformin

10. -ScienceDaily, Nov.23, 2011
-MEBO, Dec.8, 2011
-ATGCchecker, Nov, 2011

11. Induced Pluripotent Stem Cells (iPSc)

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
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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
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14. H9-NSCs
hDF-iNSCs
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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. Stem Cells, Bacteria and
Inflammatory Bowel Disease
Kim HS, Kang KS et. al.,
Gastroenterology, 2013
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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.
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18. Clean our environment
Improved our quality of life
Go back to nature
Thank you for your kind attention!