Concise review: The evolution of human pluripotent stem cell culture: from feeder cells to synthetic coatings.
Current practices to maintain human pluripotent stem cells (hPSCs), which include induced pluripotent stem cells and embryonic stem cells, in an undifferentiated state typically depend on the support of feeder cells such as mouse embryonic fibroblasts (MEFs) or an extracellular matrix such as Matrigel. Culture conditions that depend on these undefined support systems limit our ability to interpret mechanistic studies aimed at resolving how hPSCs interact with their extracellular environment to remain in a unique undifferentiated state and to make fate-changing lineage decisions. Likewise, the xenogeneic components of MEFs and Matrigel ultimately hinder our ability to use pluripotent stem cells to treat debilitating human diseases. Many of these obstacles have been overcome by the development of synthetic coatings and bioreactors that support hPSC expansion and self-renewal within defined culture conditions that are free from xenogeneic contamination. The establishment of defined culture conditions and synthetic matrices will facilitate studies to more precisely probe the molecular basis of pluripotent stem cell self-renewal and differentiation. When combined with three-dimensional cultures in bioreactors, these systems will also enable large-scale expansion for future clinical applications.
Department of Biologic & Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, USA.
L G
LG
Villa-Diaz
A M
AM
Ross
J
J
Lahann
P H
PH
Krebsbach
D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D053595:Embryonic Stem Cells / Q000166:cytology*; D005109:Extracellular Matrix; D061252:Feeder Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007797:Laminin; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011509:Proteoglycans
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen