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Title: Silica bioreplication preserves three-dimensional spheroid structures of human pluripotent stem cells and HepG2 cells

Three-dimensional (3D) cell cultures produce more in vivo-like multicellular structures such as spheroids that cannot be obtained in two-dimensional (2D) cell cultures. Thus, they are increasingly employed as models for cancer and drug research, as well as tissue engineering. It has proven challenging to stabilize spheroid architectures for detailed morphological examination. Here we overcome this issue using a silica bioreplication (SBR) process employed on spheroids formed from human pluripotent stem cells (hPSCs) and hepatocellular carcinoma HepG2 cells cultured in the nanofibrillar cellulose (NFC) hydrogel. The cells in the spheroids are more round and tightly interacting with each other than those in 2D cultures, and they develop microvilli-like structures on the cell membranes as seen in 2D cultures. Furthermore, SBR preserves extracellular matrix-like materials and cellular proteins. In conclusion, these findings provide the first evidence of intact hPSC spheroid architectures and similar fine structures to 2D-cultured cells, providing a pathway to enable our understanding of morphogenesis in 3D cultures.
 [1] ;  [1] ;  [2] ;  [3] ;  [1] ;  [1] ;  [2] ;  [1]
  1. Univ. of Helsinki (Finland). Centre for Drug Research
  2. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Advanced Materials Lab.; Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Chemical and Biomolecular Engineering
  3. Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Internal Medicine; Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials
Publication Date:
Grant/Contract Number:
FA9550-14-1-0066; CBET-1344298
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2045-2322
Nature Publishing Group
Research Org:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
OSTI Identifier: