Proliferation and enrichment of CD133+ glioblastoma cancer stem cells on 3D chitosan-alginate scaffolds

Abstract

Emerging evidence implicates cancer stem cells (CSCs) as primary determinants of the clinical behavior of human cancers, representing an ideal target for next-generation anticancer therapies. However CSCs are difficult to propagate in vitro, severely limiting the study of CSC biology and drug development. Here we report that growing cells from glioblastoma (GBM) cell lines on three dimensional (3D) porous chitosan-alginate (CA) scaffolds dramatically promotes the proliferation and enrichment of cells possessing the hallmarks of CSCs. CA scaffold-grown cells were found more tumorigenic in nude mouse xenografts than cells grown from monolayers. Growing in CA scaffolds rapidly promoted expression of genes involved in the epithelial-to-mesenchymal transition that has been implicated in the genesis of CSCs. Our results indicate that CA scaffolds have utility as a simple and inexpensive means to cultivate CSCs in vitro in support of studies to understand CSC biology and develop more effective anti-cancer therapies.

Three‑dimensional cell culture: A powerful tool in tumor research and drug discovery (Review)

“…These results indicate that 3D collagen scaffolds may provide a useful platform for anti-cancer therapeutics and CSC research. Furthermore, breast cancer stem cell expansion in PCL scaffolds (83), ovarian cancer stem cell behavior and drug resistance investigated in 3D basement membrane extract scaffolds (84) and glioma stem cells proliferating in 3D chitosan-alginate scaffolds (85) were observed in these studies, sequentially.…”

The Role of Biomaterials on Cancer Stem Cell Enrichment and Behavior

“…49 In a follow-up study, the authors demonstrated that chitosan-alginate scaffolds promoted the growth and enrichment of the CD133 + CSC population in glioblastoma cells and that the microenvironment provided by the scaffolds contributed to the more stem-like state of the cells through CD44 (a CSC marker) signaling and EMT. 15 Lastly, chitosan-alginate scaffolds have also been used to culture liver cancer cell, namely hepatocellular carcinoma (HCC), with similar results: HCC cells grown in 3D scaffolds featured greater angiogenic potential, increased expression of markers for malignancy and migration, rapid transfer into animals, and an increased resistance to chemotherapy in comparison to 2D cultures. 50 Another natural material being explored as a scaffold for cancer cells and CSC enrichment is hyaluronan (HA).…”

“…13 Unfortunately, CSCs are difficult to propagate in vitro due to the difficulty of recapitulating the necessary CSC niche, 14 which severely limits the study of CSC biology as well as therapy development. 15 Typically, CSCs are propagated and studied in vivo or in tumor spheroid models grown on non-adhesive substrates and serum-free media. 16 Here, we suggest that improved cancer models will further support CSC enrichment and that such in vitro models will include clever biomaterial designs.…”

Synthesis of nanosilver loaded chitosan/poly(acrylamide-co-itaconic acid) based inter-polyelectrolyte complex films for antimicrobial applications

“…Chitosan, a de-acetylated product of chitin, is a biocompatible polysaccharide (Hari & Nair, 2016;Rodrigues, Dionísio, Remuñán López, Grenha, 2012;Ravindranathan, Koppolu, Smith, Zaharoff, 2016) with a number of biomedical applications such as wound dressing (Anithaa, Sowmyaa & Sudheesh, 2014;Archana, Singh, Dutta & Dutta, 2015;Dina & Sahl, 2009;Dutta & Dutta, 2015;Harkins, Duri, Kloth & Tran, 2014;Keong & Halim, 2009), drug delivery (Gowda et al, 2015;Tajmir-Riahi, NafisiSh, Sanyakamdhorn & Agudelo et al, 2014), tissue re-generation, artificial cartilage (Nettles, Elder, Gilbert, 2002;Gowda et al, 2015;Tajmir-Riahi, NafisiSh, Sanyakamdhorn & Agudelo et al, 2014), porous scaffolds (Ahmed et al, 2015;Baniasadi, Ramazani & Mashayekhan, 2014;Kievit et al, 2014;Rahman, Pervez, Mubarak, Khan, 2013) etc. Chitosan, due to its cationic nature in the dissolved state, has also been exploited to prepare its IPC matrix with appropriate anionic polymers for various biomedical applications (Sakloetsakun, Preechagoon, Bernkop-Schnürch & Pongjanyakul, 2016;Kassem, Ismail, Naggar, & Aboulmagd, 2015;Argin, Kofinas & Lo, 2014).…”