Tailored Integrin-Extracellular Matrix Interactions to Direct Human Mesenchymal Stem Cell Differentiation

被引:148
|
作者
Frith, Jessica Ellen [1 ]
Mills, Richard James [1 ]
Hudson, James Edward [1 ]
Cooper-White, Justin John [1 ,2 ]
机构
[1] Univ Queensland, Tissue Engn & Microfluid Lab, Australian Inst Bioengn & Nanotechnol, St Lucia, Qld 4072, Australia
[2] Univ Queensland, Sch Chem Engn, Fac Engn Architecture & IT, St Lucia, Qld, Australia
基金
澳大利亚研究理事会;
关键词
HUMAN BONE-MARROW; IN-VITRO ANALYSIS; OSTEOGENIC DIFFERENTIATION; CHONDROGENIC DIFFERENTIATION; ENDOTHELIAL-CELLS; GENE-EXPRESSION; ADIPOSE-TISSUE; STROMAL CELLS; COLLAGEN-I; ADHESION;
D O I
10.1089/scd.2011.0615
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Integrins provide the primary link between mesenchymal stem cells (MSCs) and their surrounding extracellular matrix (ECM), with different integrin pairs having specificity for different ECM molecules or peptide sequences contained within them. It is widely acknowledged that the type of ECM present can influence MSC differentiation; however, it is yet to be determined how specific integrin-ECM interactions may alter this or how they change during differentiation. We determined that human bone marrow-derived mesenchymal stem cells (hMSCs) express a broad range of integrins in their undifferentiated state and show a dramatic, but transient, increase in the level of alpha 5 integrin on day 7 of osteogenesis and an increase in alpha 6 integrin expression throughout adipogenesis. We used a nonfouling polystyrene-block-poly(ethylene oxide)-copolymer (PS-PEO) surface to present short peptides with defined integrin-binding capabilities (RGD, IKVAV, YIGSR, and RETTAWA) to hMSCs and investigate the effects of such specific integrin ECM contacts on differentiation. hMSCs cultured on these peptides displayed different morphologies and had varying abilities to differentiate along the osteogenic and adipogenic lineages. The peptide sequences most conducive to differentiation (IKVAV for osteogenesis and RETTAWA and IKVAV for adipogenesis) were not necessarily those that were bound by those integrin subunits seen to increase during differentiation. Additionally, we also determined that presentation of RGD, which is bound by multiple integrins, was required to support long-term viability of hMSCs. Overall we confirm that integrin ECM contacts change throughout hMSC differentiation and show that surfaces presenting defined peptide sequences can be used to target specific integrins and ultimately influence hMSC differentiation. This platform also provides information for the development of biomaterials capable of directing hMSC differentiation for use in tissue engineering therapies.
引用
收藏
页码:2442 / 2456
页数:15
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