TY - JOUR
T1 - Complex tumor spheroid formation and one‐step cancer‐ associated fibroblasts purification from hepatocellular carcinoma tissue promoted by inorganic surface topography
AU - Dituri, Francesco
AU - Centonze, Matteo
AU - Berenschot, Erwin J.W.
AU - Tas, Niels R.
AU - Susarrey-Arce, Arturo
AU - Krol, Silke
N1 - Funding Information:
S.K. received financial funding by the Italian Ministero della salute in form of the grant RC2021.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12
Y1 - 2021/12
N2 - In vitro cell models play important roles as testbeds for toxicity studies, drug development, or as replacements in animal experiments. In particular, complex tumor models such as hepatocellular carcinoma (HCC) are needed to predict drug efficacy and facilitate translation into clinical practice. In this work, topographical features of amorphous silicon dioxide (SiO2) are fabricated and tested for cell culture of primary HCC cells and cell lines. The topographies vary from pyramids to octahedrons to structures named fractals, with increased hierarchy and organized in periodic arrays (square or Hexagonal). The pyramids were found to promote complex 2D/3D tissue formation from primary HCC cells. It was found that the 2D layer was mainly composed of cancer‐associated fibroblasts (CAFs), while the 3D spheroids were composed of tumor cells enwrapped by a CAF layer. Compared with conventional protocols for 3D cultures, this novel approach mimics the 2D/3D complexity of the original tumor by invading CAFs and a microtumor. Topographies such as octahedrons and fractals exclude tumor cells and allow one‐step isolation of CAFs even directly from tumor tissue of patients as the CAFs migrate into the structured substrate. Cell lines form spheroids within a short time. The presented inorganic topographical surfaces stimulate complex spheroid formation while avoiding additional biological scaffolds and allowing direct visualization on the substrate.
AB - In vitro cell models play important roles as testbeds for toxicity studies, drug development, or as replacements in animal experiments. In particular, complex tumor models such as hepatocellular carcinoma (HCC) are needed to predict drug efficacy and facilitate translation into clinical practice. In this work, topographical features of amorphous silicon dioxide (SiO2) are fabricated and tested for cell culture of primary HCC cells and cell lines. The topographies vary from pyramids to octahedrons to structures named fractals, with increased hierarchy and organized in periodic arrays (square or Hexagonal). The pyramids were found to promote complex 2D/3D tissue formation from primary HCC cells. It was found that the 2D layer was mainly composed of cancer‐associated fibroblasts (CAFs), while the 3D spheroids were composed of tumor cells enwrapped by a CAF layer. Compared with conventional protocols for 3D cultures, this novel approach mimics the 2D/3D complexity of the original tumor by invading CAFs and a microtumor. Topographies such as octahedrons and fractals exclude tumor cells and allow one‐step isolation of CAFs even directly from tumor tissue of patients as the CAFs migrate into the structured substrate. Cell lines form spheroids within a short time. The presented inorganic topographical surfaces stimulate complex spheroid formation while avoiding additional biological scaffolds and allowing direct visualization on the substrate.
KW - Cancer‐associated fibroblast
KW - Cell culture
KW - Hepatocellular carcinoma
KW - In vitro tumor models
KW - Structured surface
KW - Tumor spheroids
KW - UT-Gold-D
UR - http://www.scopus.com/inward/record.url?scp=85119965236&partnerID=8YFLogxK
U2 - 10.3390/nano11123233
DO - 10.3390/nano11123233
M3 - Article
AN - SCOPUS:85119965236
SN - 2079-4991
VL - 11
JO - Nanomaterials
JF - Nanomaterials
IS - 12
M1 - 3233
ER -