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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2011, Vol. 31 Issue (03): 81-86    
综述     
微流控芯片在干细胞研究中的应用
赵振礼, 蔡绍皙, 戴小珍
重庆大学生物工程学院 生物流变科学与技术教育部重点实验室 重庆 400030
Microfluidic Chip Application in Stem Cell Research
ZHAO Zhen-li, CAI Shao-xi, DAI Xiao-zhen
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China
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摘要:

干细胞以其多潜能性和自我更新能力成为人类早期胚胎研究、干细胞治疗和组织工程修复中的主要细胞来源和种子细胞。但传统细胞研究方法难以提供干细胞生长和分化所需的复杂多层次的微环境,使研究结果与体内真实情况相差甚远,尽可能模拟和精确调控干细胞培养微环境,进而控制干细胞自我更新或分化命运,成干细胞研究的难点。微流控芯片可以更真实地模拟干细胞小生境(niche);实时可控的对单个干细胞加载剪切力和生长因子;其透明的装置可对细胞行为进行跟踪观察等研究细胞微环境中占有优势,从而受到越来越多干细胞研究者的关注。结合对微流控技术研究经验,对干细胞微环境构建所需条件进行了综述,总结了微流控在干细胞研究中所取得的成果,并展望了微流控技术在干细胞研究中的应用前景。

关键词: 干细胞微环境微流控芯片微流控技术可溶性因子机械力体外模拟调控三维培养    
Abstract:

The stem cell has become an ideal supply of cells for tissue engineering and cellular therapies for its’ capacity of long-term self-renewal and multipotency-the ability to differentiate into one or more specialized cell types properties. These approaches require a readily available source of stem cell outside a living body. But the stem cell's microenvironment hasn't been clearly defined for its' multiplicity and complexity, and the conventional culture cell method's limitation also dedicate for it. The stem cell's self-renewal or differentiation fate couldn't be controlled outside a living body with current stem cell research method. As the stem cell is very sensitive for the microenvironment change, precisely mimic and control the stem cell microenvironment that control the stem cell's self-renewal or differentiation fate has become the difficulty in stem cell research. With the introduction of microfluidics into cell culture technology, it is possible that mimic the stem cells’ in vivo microenvironment in vitro. For it can culture stem cell in 3D microenvironment; precisely control the various factors and study their influence on the stem cell fate. Furthermore microfluidic chip can also be made transparent and monitor the stem cells real time by imaging.In the microfluidics and the blood vessel endothelial progenitor cell, review the microenvironment that the stem cell needed and enumerate the advantages of microfluidic technology, summary some successful research findings for the stem cell research inside microfluidics. And the prospect of this technology for the stem cell microenvironment and for other applications was made.

Key words: Stem cells&rsquo    microenvironment    Microfluidic chip    Microtechnology    Soluble factors    Mechanical force    Mimic and regulate in vitro    3-dimensional cell culture
收稿日期: 2010-11-08 出版日期: 2011-04-01
ZTFLH:  Q6  
基金资助:

国家自然科学基金(10872224, 81000067)、"211工程"三期建设(S-09104)资助项目

通讯作者: 蔡绍皙     E-mail: sxcai@cqu.edu.cn
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赵振礼, 蔡绍皙, 戴小珍. 微流控芯片在干细胞研究中的应用[J]. 中国生物工程杂志, 2011, 31(03): 81-86.

ZHAO Zhen-li, CAI Shao-xi, DAI Xiao-zhen. Microfluidic Chip Application in Stem Cell Research. China Biotechnology, 2011, 31(03): 81-86.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/        https://manu60.magtech.com.cn/biotech/CN/Y2011/V31/I03/81

[1] Leclerc E, Sakai Y, Fujii T. Cell culture in 3-dimensional microfluidic structure of PDMS (polydimethylsiloxane). Biomedical Microdevices, 2003, 5(2): 109-114.
[2] Yi C Q, Li C W, Ji S L, et al. Microfluidics technology for manipulation and analysis of biological cells,2006, 560(1-2): 1-23.
[3] Andersson H, van den Berg A. Microfluidic devices for cellomics: a review. Sensors and Actuators B-Chemical, 2003, 92(3): 315-325.
[4] Villa-Oiaz L G, Torisawa Y, Uchida T,et al. Microfluidic culture of single human embryonic stem cell colonies. Lab Chip, 2009,9(12):1744-1755.
[5] van Noort D, Ong S M, Zhang C, et al. Stem cells in microfluidics. Biotechnol Prog, 2009, 25(1): 52-60.
[6] Weissman I L. Stem cells: units of development, units of regeneration, and units in evolution. Cell, 2000, 100(1): 157-168.
[7] Imreh M P, Gertow K, Cedervall J, et al. In vitro culture conditions favoring selection of chromosomal abnormalities in human ES cells. Journal of Cellular Biochemistry, 2006, 99(2): 508-516.
[8] Discher D E, Mooney D J, Zandstra P W. Growth Factors, Matrices, and Forces Combine and Control Stem Cells,2009, 324(5935): 1673-1677.
[9] Gupta K, Kim D H, Ellison D, et al. Lab-on-a-chip devices as an emerging platform for stem cell biology. Lab On a Chip, 2010, 10(16): 2019-2031.
[10] Chin V I, Taupin P, Sanga S, et al. Microfabricated platform for studying stem cell fates. Biotechnology and Bioengineering, 2004, 88(3): 399-415.
[11] Yin H, Killeen K, Brennen R, et al. Microfluidic chip for peptide analysis with an integrated HPLC column, sample enrichment column, and nanoelectrospray tip. Analytical Chemistry, 2005, 77(2): 527-533.
[12] Randall G C, Doyle P S. Permeation-driven flow in poly(dimethylsiloxane) microfluidic devices. Proc Natl Acad Sci U S A, 2005, 102(31): 10813-10818.
[13] Mcdonald J C, Duffy D C, Anderson J R, et al. Fabrication of microfluidic systems in poly(dimethylsiloxane). Electrophoresis, 2000, 21(1): 27-40.
[14] van Noort D, Ong S M, Zhang C, et al. Stem cells in microfluidics. Biotechnology Progress, 2009, 25(1): 52-60.
[15] Walker G M, Zeringue H C, Beebe D J. Microenvironment design considerations for cellular scale studies. Lab on a Chip, 2004, 4(2): 91-97.
[16] Huang C P, Lu J, Seon H, et al. Engineering microscale cellular niches for three-dimensional multicellular co-cultures. Lab On a Chip, 2009, 9(12): 1740-1748.
[17] Viravaidya K, Shuler M L. Incorporation of 3T3-L1 cells to mimic bioaccumulation in a microscale cell culture analog device for toxicity studies. Biotechnol Prog, 2004, 20(2): 590-597.
[18] Burdick J A, Vunjak-Novakovic G. Engineered microenvironments for controlled stem cell differentiation. Tissue Eng Part A, 2009, 15(2): 205-219.
[19] Scadden D T. The stem-cell niche as an entity of action. Nature, 2006, 441(7097): 1075-1079.
[20] Jones D L, Wagers A J. No place like home: anatomy and function of the stem cell niche. Nature Reviews Molecular Cell Biology, 2008, 9(1): 11-21.
[21] Abbott A. Cell culture: Biology's new dimension. Nature, 2003, 424(6951): 870-872.
[22] Dawson E, Mapili G, Erickson K, et al. Biomaterials for stem cell differentiation. Adv Drug Deliv Rev, 2008, 60(2): 215-228.
[23] Toh Y C, Zhang C, Zhang J, et al. A novel 3D mammalian cell perfusion-culture system in microfluidic channels. Lab On a Chip, 2007, 7(3): 302-309.
[24] Ong S M, Zhang C, Toh Y C, et al. A gel-free 3D microfluidic cell culture system. Biomaterials, 2008, 29(22): 3237-3244.
[25] Zaari N, Rajagopalan P, Kim S K, et al. Photopolymerization in microfluidic gradient generators: Microscale control of substrate compliance to manipulate cell response. Advanced Materials, 2004, 16(23-24): 2133.
[26] Korin N, Bransky A, Dinnar U, et al. Periodic "flow-stop" perfusion microchannel bioreactors for mammalian and human embryonic stem cell long-term culture. Biomed Microdevices, 2009, 11(1): 87-94.
[27] Chung B G, Flanagan L A, Rhee S W, et al. Human neural stem cell growth and differentiation in a gradient-generating microfluidic device. Lab On a Chip, 2005, 5(4): 401-406.
[28] Flaim C J, Teng D, Chien S, et al. Combinatorial signaling microenvironments for studying stem cell fate. Stem Cells and Development, 2008, 17(1): 29-39.
[29] Ju X, Li D, Gao N, et al. Hepatogenic differentiation of mesenchymal stem cells using microfluidic chips. Biotechnology Journal, 2008, 3(3): 383-391.
[30] Kim L, Vahey M D, Lee H Y, et al. Microfluidic arrays for logarithmically perfused embryonic stem cell culture. Lab On a Chip, 2006, 6(3): 394-406.
[31] Ponte A L, Marais E, Gallay N, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells, 2007, 25(7): 1737-1745.
[32] Hung P J, Lee P J, Sabounchi P, et al. Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. Biotechnology and Bioengineering, 2005, 89(1): 1-8.
[33] Kanichai M, Ferguson D, Prendergast P J, et al. Hypoxia promotes chondrogenesis in rat mesenchymal stem cells: a role for AKT and hypoxia-inducible factor (HIF)-1alpha. Journal of Cellular Physiology, 2008, 216(3): 708-715.
[34] Lucchetta E M, Lee J H, Fu L A, et al. Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics. Nature, 2005, 434(7037): 1134-1138.
[35] Kim S M, Lee S H, Suh K Y. Cell research with physically modified microfluidic channels: a review. Lab On a Chip, 2008, 8(7): 1015-1023.
[36] Angele P, Yoo J U, Smith C, et al. Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. Journal of Orthopaedic Research, 2003, 21(3): 451-457.
[37] Blagovi c ' K, Przybyta L, Toch Y C, et al. Microfluidic perfusion for modulating stem cell diffusible signaling. Microsysiems Technology Laboratories Annual Research Report, 2009.
[38] Plouffe B D, Kniazeva T, Mayer J J, et al. Development of microfluidics as endothelial progenitor cell capture technology for cardiovascular tissue engineering and diagnostic medicine. Faseb Journal, 2009, 23(10): 3309-3314.
[39] Park S H, Sim W Y, Park S W, et al. An electromagnetic compressive force by cell exciter stimulates chondrogenic differentiation of bone marrow-derived mesenchymal stem cells. Tissue Engineering, 2006, 12(11): 3107-3117.
[40] Metallo C M, Vodyanik M A, de Pablo J J, et al. The response of human embryonic stem cell-derived endothelial cells to shear stress. Biotechnology and Bioengineering, 2008, 100(4): 830-837.
[41] Saha S, Ji L, de Pablo J J, et al. Inhibition of human embryonic stem cell differentiation by mechanical strain. Journal of Cellular Physiology, 2006, 206(1): 126-137.
[42] Zhong J F, Chen Y, Marcus J S, et al. A microfluidic processor for gene expression profiling of single human embryonic stem cells. Lab On a Chip, 2008, 8(1): 68-74.

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