Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells.
Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in culture; however, present methods to clonally grow them are inefficient and poorly defined for genetic manipulation and therapeutic purposes. Here we develop the first chemically defined, xeno-free, feeder-free synthetic substrates to support robust self-renewal of fully dissociated human embryonic stem and induced pluripotent stem cells. Material properties including wettability, surface topography, surface chemistry and indentation elastic modulus of all polymeric substrates were quantified using high-throughput methods to develop structure-function relationships between material properties and biological performance. These analyses show that optimal human embryonic stem cell substrates are generated from monomers with high acrylate content, have a moderate wettability and employ integrin alpha(v)beta(3) and alpha(v)beta(5) engagement with adsorbed vitronectin to promote colony formation. The structure-function methodology employed herein provides a general framework for the combinatorial development of synthetic substrates for stem cell culture.
Mei
Ying
Y
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Saha
Krishanu
K
Bogatyrev
Said R
SR
Yang
Jing
J
Hook
Andrew L
AL
Kalcioglu
Z Ilke
ZI
Cho
Seung-Woo
SW
Mitalipova
Maisam
M
Pyzocha
Neena
N
Rojas
Fredrick
F
Van Vliet
Krystyn J
KJ
Davies
Martyn C
MC
Alexander
Morgan R
MR
Langer
Robert
R
Jaenisch
Rudolf
R
Anderson
Daniel G
DG
D001672:Biocompatible Materials / Q000737:chemistry*; D002454:Cell Differentiation; D002478:Cells, Cultured; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism
D001672:Biocompatible Materials