An alginate-based platform for cancer stem cell research.
As the primary determinants of the clinical behaviors of human cancers, the discovery of cancer stem cells (CSCs) represents an ideal target for novel anti-cancer therapies (Kievit et al., 2014). Notably, CSCs are difficult to propagate in vitro, which severely restricts the study of CSC biology and the development of therapeutic agents. Emerging evidence indicates that CSCs rely on a niche that controls their differentiation and proliferation, as is the case with normal stem cells (NSCs). Replicating the in vivo CSC microenvironment in vitro using three-dimensional (3D) porous scaffolds can provide means to effectively generate CSCs, thus enabling the discovery of CSC biology. This paper presents our study on a novel alginate-based platform for mimicking the CSC niche to promote CSC proliferation and enrichment. In this study, we used a versatile mouse 4T1 breast cancer model to independently evaluate the matrix parameters of a CSC niche - including the material's mechanical properties, cytokine immobilization, and the composition of the extracellular matrix's (ECM's) molecular impact - on CSC proliferation and enrichment. On this basis, the optimal stiffness and concentration of hyaluronic acid (HA), as well as epidermal growth factor and basic fibroblast growth factor immobilization, were identified to establish the platform for mimicking the 4T1 breast CSCs (4T1 CSCs) niche. The 4T1 CSCs obtained from the platform show increased expression of the genes involved in breast CSC and NSC, as compared to general 2D or 3D culture, and 4T1 CSCs were also demonstrated to have the ability to quickly form a subcutaneous tumor in homologous Balb/c mice in vivo. In addition, the platform can be adjusted according to different parameters for CSC screening. Our results indicate that our platform offers a simple and efficient means to isolate and enrich CSCs in vitro, which can help researchers better understand CSC biology and thus develop more effective therapeutic agents to treat cancer.



As the primary determinants of the clinical behaviors of human cancers, the discovery of cancer stem cells (CSCs) represents an ideal target for novel anti-cancer therapies. However, CSCs are difficult to propagate in vitro, which severely restricts the study of CSC biology and the development of therapeutic agents. Emerging evidence indicates that CSCs rely on a niche that controls their differentiation and proliferation, as is the case with normal stem cells (NSCs). Replicating the in vivo CSC microenvironment in vitro using three-dimensional (3D) porous scaffolds can provide means to effectively generate CSCs, thus enabling the discovery of CSC biology. In our study, a novel alginate-based platform were developed for mimicking the CSC niche to promote CSC proliferation and enrichment.
Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, PR China.
Shu-Pei
SP
Qiao
Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, PR China.
Yu-Fang
YF
Zhao
Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, PR China.
Chun-Feng
CF
Li
Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, PR China.
Yan-Bin
YB
Yin
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, PR China.
Qing-Yuan
QY
Meng
Division of Biomedical Engineering and Nanomedicine Research, National Health Research Institutes, Miaoli, Taiwan, ROC; Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan, ROC.
Feng-Huei
FH
Lin
Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, PR China.
Yi
Y
Liu
Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, PR China.
Xiao-Lu
XL
Hou
Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, PR China.
Kai
K
Guo
Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, Canada; Department of Mechanical Engineering, University of Saskatchewan, Saskatoon, Canada.
Xiong-Biao
XB
Chen
Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, PR China. Electronic address: tianweiming@hit.edu.cn.
Wei-Ming
WM
Tian
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D055767:Immobilized Proteins / Q000494:pharmacology; D055595:Mechanical Phenomena; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology; D055153:Stem Cell Niche / Q000187:drug effects; D057905:Stem Cell Research; D015854:Up-Regulation / Q000187:drug effects
D000464:Alginates; D016207:Cytokines; D006603:Hexuronic Acids; D055767:Immobilized Proteins; D006859:Hydrogen; D020723:Glucuronic Acid; D006820:Hyaluronic Acid
Alginate; Cancer stem cell; Hyaluronic acid; Niche; Platform