미세접촉인쇄법을 이용한 지방세포 칩 제작

김지용; 정헌호; 이창수; Gi Yong Kim; Heon-Ho Jeong; Chang-Soo Lee; 노창현

Korean Chemical Engineering Research, Vol.54, No.2, 223-228, April, 2016

DOI10.9713/kcer.2016.54.2.223 Export Citation

미세접촉인쇄법을 이용한 지방세포 칩 제작

Simple Fabrication of Adipocyte Cell Chip Using Micropatterning

김지용^{1, 2}, 정헌호², 이창수 ^{2, †}, ^{1, †}

¹한국원자력연구원 첨단방사선연구소 생명공학연구부, 56212 전북 정읍시 신정동 1266
²충남대학교 공과대학 화학공학과, 34134 대전광역시 궁동 220

Gi Yong Kim^{1, 2}, Heon-Ho Jeong², Chang-Soo Lee^{2, †}, and 노창현^{1, 3, †}

¹Division of Biotechnology, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), 29, Geumgu-gil, Jeongeup, Jeonbuk, 56212, Korea
²Department of Chemical Engineering, Chungnam National University, 220, Gung-Dong, Yuseong-gu, Daejeon, 34134, Korea
³, Korea

E-mail:,

초록

본 논문은 PDMS을 기반으로 한 미세접촉인쇄법을 사용하여 보다 효율적으로 지방세포를 선택적으로 배양접시에 부착시켰으며 패터닝 된 배양접시에서 지방세포가 빠르게 지방분화를 가능하게 하였다. PDMS을 이용한 선택적 표면처리 방법은 기존의 세포칩 제작과 달리 소량의 유기용매사용, 저가의 장비 사용, 또한 효율적으로 특정 지역 안에서 지방세포를 고정화하고 성장시킬 수 있으며 이를 통해 지방세포의 생리학적 상태를 손쉽게 관찰할 수 있는 분석 기술로 활용된다. 이렇게 구성된 지방세포칩 위에 대표적인 비만 억제제 약물인 Orlistat을 0.2 μM~5.0 μM 농도로 처리하였을 때 대조군에 비하여 최대 26.5%의 억제 효과가 나타남을 확인하였다. 따라서, 본 논문에서 제안하는 방법을 통하여 다양한 비만 억제제 약물 탐색을 위한 세포칩으로 활용이 가능할 것으로 기대된다.

In this study, we described a simple and facile method to generate uniform microwells poly(dimethyl siloxane) (PDMS) microstamps through micro-molding for efficient, rapid and reliable cell patterning of adipocyte differentiation. In contrast to the conventional methods, the microstamp technologies are low expensive, non-toxic, and using a small amount of solution. Recently, Orlistat known as tetrahydrolipstatin is a prescription drug designed to treat obesity which is used to aid in weight loss and help to reduce overweight obesity. Here, 3T3-L1 cells were treated under various concentration manners of Orlistat 0.2 μM~5.0 μM. and it was confirmed maximum 26.5% inhibition activity compared to control. Thus, we elucidated this platform can be used for the real-time analyzing of cell proliferation, adipocyte differentiation for evaluation of anti-obesity agents on cell chip. Furthermore, we except that this platform technology designed here might be readily be expanded to discover a wider variety of anti-obesity agents.

Keywords:Micropatterning;Anti-obesity agents;Screening;Orlistat

[References]

Marcelin G, Chua S, Curr. Opin. Pharm., 10(5), 588 (2010)
Cooke D, Bloom S, Nat. Rev. Drug Discovery, 5(11), 919 (2006)
Kim HC, Kim MR, Korean J. Human Ecology, 19(1), 157 (2010)
Kim TH, You G, Korean J. internal Medicine, 68(4), 347 (2005)
Finkelstein EA, Trogdon JG, Brown DS, Allaire BT, Dellea PS, Kamal-Bahl SJ, Obesity, 16(8), 1843 (2008)
Roh C, Choi NH, Park HR, Jung U, Jo SK, Eur. J. Lipid. Sci. Tech., 112(12), 1384 (2010)
Muls E, Kolanowski J, Scheen A, Van Gaal L, International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity, 25(11), 1713 (2001)
Jeong HH, Noh YM, Jang SC, Lee CS, Korean Chem. Eng. Res., 52(2), 141 (2014)
Rosenthal A, Macdonald A, Voldman J, Biomaterials, 28(21), 3208 (2007)
Yamazoe H, Uemura T, Tanabe T, Langmuir, 24(16), 8402 (2008)
Neff JA, Tresco P, Caldwell K, Biomaterials, 20(23), 2377 (1999)
Park BS, Kim WY, Yoon KB, Korean J. Chem. Eng., 31(1), 172 (2014)
Choi JH, Kim GM, J. Korean Society for Precision Engineering, 30(2), 236 (2013)
Tontonoz P, Hu E, Spiegelman BM, Cell, 79(7), 1147 (1994)
Nishizawa M, Takahashi A, Kaji H, Matsue T, Chem. Lett., 31(9), 904 (2002)
Taniguchi N, Miyoshi E, Jianguo G, Honke K, Matsumoto A, Curr. Opin. Struct. Biol., 16(5), 561 (2006)
Dube DH, Bertozzi CR, Nat. Rev. Drug Discovery, 4(6), 477 (2005)
Jeong HH, Kim YG, Jang SC, Yi H, Lee CS, Lab Chip, 12(18), 3290 (2012)
Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM, Molecular Cell, 4(4), 611 (1999)
Hwang J, Wang J, Morazzoni P, Hodis HN, Sevanian A, Free Radic. Biol. Med., 34(10), 1271 (2003)
Lee HB, Polym. Sci. Technol., 5(6), 566 (1994)
Ramirez-Zacarias J, Castro-Munozledo F, Kuri-Harcuch W, Histochemistry, 97(6), 493 (1992)
Guerciolini R, International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity, 21, S12 (1997)
Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L, Diabetes Care, 27(1), 155 (2004)

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[2] Cooke D, Bloom S, Nat. Rev. Drug Discovery, 5(11), 919 (2006)

[3] Kim HC, Kim MR, Korean J. Human Ecology, 19(1), 157 (2010)

[4] Kim TH, You G, Korean J. internal Medicine, 68(4), 347 (2005)

[5] Finkelstein EA, Trogdon JG, Brown DS, Allaire BT, Dellea PS, Kamal-Bahl SJ, Obesity, 16(8), 1843 (2008)

[6] Roh C, Choi NH, Park HR, Jung U, Jo SK, Eur. J. Lipid. Sci. Tech., 112(12), 1384 (2010)

[7] Muls E, Kolanowski J, Scheen A, Van Gaal L, International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity, 25(11), 1713 (2001)

[8] Jeong HH, Noh YM, Jang SC, Lee CS, Korean Chem. Eng. Res., 52(2), 141 (2014)

[9] Rosenthal A, Macdonald A, Voldman J, Biomaterials, 28(21), 3208 (2007)

[10] Yamazoe H, Uemura T, Tanabe T, Langmuir, 24(16), 8402 (2008)

[11] Neff JA, Tresco P, Caldwell K, Biomaterials, 20(23), 2377 (1999)

[12] Park BS, Kim WY, Yoon KB, Korean J. Chem. Eng., 31(1), 172 (2014)

[13] Choi JH, Kim GM, J. Korean Society for Precision Engineering, 30(2), 236 (2013)

[14] Tontonoz P, Hu E, Spiegelman BM, Cell, 79(7), 1147 (1994)

[15] Nishizawa M, Takahashi A, Kaji H, Matsue T, Chem. Lett., 31(9), 904 (2002)

[16] Taniguchi N, Miyoshi E, Jianguo G, Honke K, Matsumoto A, Curr. Opin. Struct. Biol., 16(5), 561 (2006)

[17] Dube DH, Bertozzi CR, Nat. Rev. Drug Discovery, 4(6), 477 (2005)

[18] Jeong HH, Kim YG, Jang SC, Yi H, Lee CS, Lab Chip, 12(18), 3290 (2012)

[19] Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM, Molecular Cell, 4(4), 611 (1999)

[20] Hwang J, Wang J, Morazzoni P, Hodis HN, Sevanian A, Free Radic. Biol. Med., 34(10), 1271 (2003)

[21] Lee HB, Polym. Sci. Technol., 5(6), 566 (1994)

[22] Ramirez-Zacarias J, Castro-Munozledo F, Kuri-Harcuch W, Histochemistry, 97(6), 493 (1992)

[23] Guerciolini R, International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity, 21, S12 (1997)

[24] Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L, Diabetes Care, 27(1), 155 (2004)