Autor: |
Cerchiari A; 1UC Berkeley-UCSF Graduate Program in Bioengineering, Department of Bioengineering, University of California Berkeley, Berkeley, California.; 6Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California., Garbe JC; 2Lawrence Berkeley National Lab, Berkeley, California., Todhunter ME; 3TETRAD Graduate Program, University of California San Francisco, San Francisco, California.; 4Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California., Jee NY; 4Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California.; 5Chemistry and Chemical Biology Graduate Program, University of California San Francisco, San Francisco, California., Pinney JR; 1UC Berkeley-UCSF Graduate Program in Bioengineering, Department of Bioengineering, University of California Berkeley, Berkeley, California.; 6Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California., LaBarge MA; 2Lawrence Berkeley National Lab, Berkeley, California., Desai TA; 1UC Berkeley-UCSF Graduate Program in Bioengineering, Department of Bioengineering, University of California Berkeley, Berkeley, California.; 5Chemistry and Chemical Biology Graduate Program, University of California San Francisco, San Francisco, California.; 6Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California., Gartner ZJ; 1UC Berkeley-UCSF Graduate Program in Bioengineering, Department of Bioengineering, University of California Berkeley, Berkeley, California.; 3TETRAD Graduate Program, University of California San Francisco, San Francisco, California.; 4Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California.; 7University of California San Francisco Center for Systems and Synthetic Biology, San Francisco, California. |
Abstrakt: |
Patterned three-dimensional (3D) cell culture models aim to more accurately represent the in vivo architecture of a tissue for the purposes of testing drugs, studying multicellular biology, or engineering functional tissues. However, patterning 3D multicellular structures within very soft hydrogels (<500 Pa) that mimic the physicochemical environment of many tissues remains a challenge for existing methods. To overcome this challenge, we use a Sacrificial Micromolding technique to temporarily form spatially and geometrically defined 3D cell aggregates in degradable scaffolds before transferring and culturing them in a reconstituted extracellular matrix. Herein, we demonstrate that Sacrificial Micromolding (1) promotes cyst formation and proper polarization of established epithelial cell lines, (2) allows reconstitution of heterotypic cell-cell interactions in multicomponent epithelia, and (3) can be used to control the lumenization-state of epithelial cysts as a function of tissue size. In addition, we discuss the potential of Sacrificial Micromolding as a cell-patterning tool for future studies. |