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Investigate Cellular Responses for Environmental Cues Qian Wang Department of Chemistry and Biochemistry, and Nanocenter University of South Carolina,

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Presentation on theme: "Investigate Cellular Responses for Environmental Cues Qian Wang Department of Chemistry and Biochemistry, and Nanocenter University of South Carolina,"— Presentation transcript:

1 Investigate Cellular Responses for Environmental Cues Qian Wang Department of Chemistry and Biochemistry, and Nanocenter University of South Carolina, SC, USA

2 Cell shape determines fate of stem cells Mrksich M., et al. PNAS, 2010, 16, 4872-4877 Star shape and flower shape expressed different differentiation profile Flower shape promoted adipogenesis Star shape promoted osteogenesis Flower Star

3 ECM Mimetic Substrates Abrams, G. A., et al., Cell Tissue Res, 2000, 299, 39-46 Kim, D. H. et al., PNAS, 2010, 107,565-570 Roohani-Esfahani, S.I., et al., Biomaterials, 2010, 31, 5498-5509 Pham, Q. P. et al., Tissue Eng, 2006, 12, 1197-211 50um Natural ECM architecture ECM mimetic substrates

4 Nature 414:105, 2001 Models of Tumor Heterogeneity

5 Are We Targeting the Right Cancer Cells? Sarkar, B. ; Dosch, J., et al. Chem. Rev. 2009, 109, 3200–3208 Major Challenges: Lack of universal biomarker Lack of In vitro cell culture model Major Challenges: Lack of universal biomarker Lack of In vitro cell culture model Nature 414:105, 2001 Dr. Hexin Chen Biologist Dr. Xinfeng Liu Mathematician

6 A Novel Breast Cancer Stem Cell Model - H6O5 Cells Lo, P. K., et al., Oncogene 2012, (doi: 10.1038/onc.2011.439)  Her2/neu induced mouse mammary tumor  Consists of a highly tumorigenic population (CSCs)  Isolated based on two integrin markers CD49f and CD61  Confirmed by its in vivo tumorigenicity CD49f CD61 Fluorescence assisted cell sorting

7 H6O5 Aligned fiber substrate Tissue culture well H6O5 Cells on Fiber Substrate Morphology EMT- associated gene expression Culture for 3- 5 days

8 Morphology of Electrospun Fiber Substrate SEM images of aligned (d = 1.8 ± 0.46 μm) and random (d = 2.0 ± 0.65 μm) Scale bar = 20 μm Poly-Caprolactone Biodegradable Cytocompatible A Aligned FiberRandom Fiber Saha. S et al.,Langmuir, 2012, 28, 2028-2034

9 Morphology of H6O5 Cells on Aligned Fiber Substrate 10x Cell attach to fiber Elongated morphology Growth, Proliferation Maintain elongated morphology 10x Green: actin cytoskeleton Blue: nuclei White arrows: underlying fiber direction, Scale bar = 40 µm ab S. Saha et al. Langmuir, 2012, 28, 2028-2034

10 Enrichment of Cancer Stem Cells Using Nano-fibrous Scaffolds S. Saha et al. Langmuir, 2012, 28, 2028-2034

11 Gene expression by qRT-PCR S. Saha et al. Langmuir, 2012, 28, 2028-2034 Enhanced Expression of EMT Markers of MCF-7 Cells

12 ALDH (Aldehyde D ehydrogenase ) Activity of MCF-7 Cells A Aligned FiberRandom Fiber Sheng Feng

13 Increased Mammosphere-Forming Capability A Aligned FiberRandom Fiber Sheng Feng

14 Increased Invasion Property of Epithelial Breast Cancers Cells Cultured On PCL Fiber A Aligned FiberRandom Fiber Sheng Feng

15 Results of MDA-MB-231 Cells Cultured from PCL Fiber A Aligned FiberRandom Fiber Sheng Feng

16 A Hypothesis of the Double-Feedback to Control the CSCs Fate A Dr. Xinfeng Liu, Hexin Chen

17 Zhongwei, Jianhua, Mike Bruckman O. D. Velev et al, Small 2006, 2, 1462 Alignment of Rod Like Nanoparticles

18 2D Alignment of Colloidal Particles Dimitrov and Nagayama, Langmuir 1996, 12, 1303

19 2D Alignment of Protein Nanoparticles Mike Bruckman, Zhongwei Niu O. D. Velev et al, Small 2006, 2, 1462

20 Jianhua Rong, Zhongwei Niu, in collaboration with Dr. Charlene Mello Controlled Alignment of Cell Growth

21 Rosamond W et al., Circulation 2008, 117 (4): e25-146 United States, 2004. Source: NCHS and NHLBI Cardiovascular Disease in USA

22 Vascular Disorders and Pathogenesis of Atherosclerosis Osterud & Bjorklid; Physiol Rev. 2003, 83, 1069-112 VSMC Proliferative form VSMC Normal form

23 Smooth Muscle Cells: Different Morphologies Lilly

24 Control Aligned Scaffold

25 Significance of the Alignment of Smooth Muscle Cells

26 Are There a Good Model to Predict/Explain The Cellular Responses to Contact Cues??

27 Are There a Good Model to Predict/Explain The Cellular Responses to Contact Cues??

28 Acknowledgments BNP Assembly: Tom Russell (UMass) Yao Lin (UConn) Alex Böker (MPI) P. Thiyagarajan (DOE) Byeongdu Lee (ANL) Lin Yang (BNL) Z. Su (CIAC, CAS) C. Xiaodong Li (USC) Wenke Zhang (Jilin U) Cell Study Hexin Chen (USC) Tara Soto-Atwood (UF) J. Potts (USC) Protein Binding Study Lukasz Lebioda (USC) Frank Berger (USC) Virus: Theo Dreher (OSU) Rick Nelson (Noble) Charlene Mello (ARL) Peter E. Prevelige (UAB) Polymeric Assembly: Mihaela Stephan (UTD) Yuan Lin (CIAC, CAS) $$$ NSF-CAREER/NSF-DMR NIH-COBRE Sloan/Camille Dreyfus DOD-ARO DOE-BES W. M. Keck Foundation SC EPSCoR Office & SCCC Wang Group: L. Andrew Lee (Postdoc) Xinrui Duan (Postdoc) Honglin Liu (Postdoc) Jun Hu (Postdoc) Pan He (Research Ass.) Dan Menasco Nikki Sitasuwan Matsepo Ramaboli Amie J. Luckanagul Wang Group Alumni: Yi Chen (Res. Professor) Gary Horvath (S. Scientist) Postdoc: K. Sivakumar S. Chittaboina V.S. Kotakadi Zhongwei Niu Qingbing Zeng Céline le Droumaguet Jianhua Rong Yuan Lin Jiangli Fan Xingjie Zan Undergraduate Student: Lisa Alexander Giang Nguyen …… Sheng Feng Hong Guan Clorissa Washington Yixing Cheng Enoch Adogla Iin Lv Gift Metavarayuth Peiyi Wang Fang Zhou (CIAC) Xia Zhao (CIAC) Limin Chen (CIAC) Many talent undergrad. Graduate Student: Hannah Barnhill Fang Xie Su Long Brandon Cash Saswat Kabisatpathy Siqi Li Mike Bruckman Gagandeep Kaur Tao Li Kai Li Chao Wang Jerry Oxsher Laying Wu Eve Suthiwangcharoen Sharmi Saha Lilly Balizan Simulation Qi Wang (USC) Xinfeng Liu (USC)


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