Hyaluronic acid hydrogen for controlled self-renewal and differentiation of human embryonic stem cells

被引:488
作者
Gerecht, Sharon
Burdick, Jason A.
Ferreira, Lino S.
Townsend, Seth A.
Langer, Robert
Vunjak-Novakovic, Gordana
机构
[1] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA
[2] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[3] Univ Coimbra, Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal
[4] Biocant Ctr Inovacao Biotecnol, P-3060197 Cantanhede, Portugal
[5] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA
关键词
scaffolds; three-dimensional cultures; vasculogenesis;
D O I
10.1073/pnas.0703723104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Control of self-renewal and differentiation of human ES cells (hESCs) remains a challenge. This is largely due to the use of culture systems that involve poorly defined animal products and do not mimic the normal developmental milieu. Routine protocols involve the propagation of hESCs on mouse fibroblast or human feeder layers, enzymatic cell removal, and spontaneous differentiation in cultures of embryoid bodies, and each of these steps involves significant variability of culture conditions. We report that a completely synthetic hydrogel matrix can support (t) long-term self-renewal of hESCs in the presence of conditioned medium from mouse embryonic fibroblast feeder layers, and (it) direct cell differentiation. Hyaluronic acid (HA) hydrogels were selected because of the role of HA in early development and feeder layer cultures of hESCs and the controllability of hydrogel architecture, mechanics, and degradation. When encapsulated in 3D HA hydrogels (but not within other hydrogels or in monolayer cultures on HA), hESCs maintained their undifferentiated state, preserved their normal karyotype, and maintained their full differentiation capacity as indicated by embryoid body formation. Differentiation could be induced within the same hydrogel by simply altering soluble factors. We therefore propose that HA hydrogels, with their developmentally relevant composition and tunable physical properties, provide a unique microenvironment for the selfrenewal and differentiation of hESCs.
引用
收藏
页码:11298 / 11303
页数:6
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