Human mesenchymal stem cell differentiation on self-assembled monolayers presenting different surface chemistries

Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Acta biomaterialia (Impact Factor: 6.03). 08/2009; 6(1):12-20. DOI: 10.1016/j.actbio.2009.07.023
Source: PubMed


Human mesenchymal stem cells (hMSCs) have tremendous potential as a cell source for regenerative medicine due to their capacity for differentiation into a wide range of connective tissue cell types. Although significant progress has been made in the identification of defined growth factor conditions to induce lineage commitment, the effect of underlying biomaterial properties on functional differentiation is far less understood. Here we conduct a systematic assessment of the role for surface chemistry on cell growth, morphology, gene expression and function during hMSC commitment along osteogenic, chondrogenic and adipogenic lineages. Using self-assembled monolayers of omega-functionalized alkanethiols on gold as model substrates, we demonstrate that biomaterial surface chemistry differentially modulates hMSC differentiation in a lineage-dependent manner. These results highlight the importance of initial biomaterial surface chemistry on long-term functional differentiation of adult stem cells, and suggest that surface properties are a critical parameter that must be considered in the design of biomaterials for stem cell-based regenerative medicine strategies.

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    • "A number of other studies also demonstrated that BMSCs induced with chondrogenic medium developed into a round phenotype and aggregated spontaneously into spheroid- or rod-like cell agglomerates. The formation of the aggregates exhibited a more intense staining for chondrogenic matrix deposition (24,25). Consistent with these studies, the present data revealed that treatment with ICA led to the formation of an increased number of and larger aggregates. "
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    ABSTRACT: Icariin (ICA), a Traditional Chinese Medicine, has been demonstrated to be a promoting compound for extracellular matrix synthesis and gene expression of chondrocytes. However, whether ICA can act as a substitute for or cooperate with growth factors to directly promote stable chondrogenesis of bone marrow mesenchymal stem cells (BMSCs) remains unknown. In the present study, rat BMSCs were cultivated in monolayer cultures with a chondrogenic medium containing transforming growth factor-β3 for 14 days; ICA was added to the same chondrogenic medium throughout the culture period at a concentration of 1×10(-6) M. Cell morphology was observed using an inverted microscope, and chondrogenic differentiation markers, including collagen II, aggrecan and SRY (sex determining region Y)-box 9 (SOX9), were detected by immunofluorescence, reverse transcription-quantitative polymerase chain reaction and western blot analysis. Hypertrophic differentiation was also analyzed using collagen I gene expression and alkaline phosphatase (ALP) activity. The results revealed that ICA was effective at forming an increased number of and larger aggregates, and significantly upregulated the mRNA expression levels and protein synthesis of collagen II, aggrecan and SOX9. Furthermore, the chondrogenic medium alone caused hypertrophic differentiation through the upregulation of collagen I gene expression and ALP activity, which was not potentiated by the presence of ICA. Thus, ICA promoted directed chondrogenic differentiation of BMSCs, but had no effect on hypertrophic differentiation. The present results also suggested that ICA may be an effective accelerant of growth factors for cartilage tissue engineering by promoting their chondrogenic differentiating effects but reducing the effect of hypertrophic differentiation.
    Experimental and therapeutic medicine 11/2014; 8(5):1528-1534. DOI:10.3892/etm.2014.1950 · 1.27 Impact Factor
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    • "These results confirmed that chemical modifications of the substrate can affect the adhesion, spreading, and osteogenic differentiation of BMSCs. The –NH2-modified surfaces promoted osteogenesis of the BMSCs in the absence of biological stimuli as previous described [24–26]. To investigate the downstream signaling pathways in BMSCs that may be involved in the regulation of osteogenesis during culture on the –NH2- and –CH3-modified substrates (the modifications with the strongest and weakest ability to promote the osteogenic differentiation of BMSCs, resp.), we focused on the key proteins of the ERK1/2 signaling pathway, as suggested by earlier studies implicating these pathways [37]. "
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    ABSTRACT: The current study examined the influence of culture substrates modified with the functional groups -OH, -COOH, -NH2, and -CH3 using SAMs technology, in conjunction with TAAB control, on the osteogenic differentiation of rabbit BMSCs. The CCK-8 assay revealed that BMSCs exhibited substrate-dependent cell viability. The cells plated on -NH2- and -OH-modified substrates were well spread and homogeneous, but those on the -COOH- and -CH3-modified substrates showed more rounded phenotype. The mRNA expression of BMSCs revealed that -NH2-modified substrate promoted the mRNA expression and osteogenic differentiation of the BMSCs. The contribution of ERK1/2 signaling pathway to the osteogenic differentiation of BMSCs cultured on the -NH2-modified substrate was investigated in vitro. The -NH2-modified substrate promoted the expression of integrins; the activation of FAK and ERK1/2. Inhibition of ERK1/2 activation by PD98059, a specific inhibitor of the ERK signaling pathway, blocked ERK1/2 activation in a dose-dependent manner, as revealed for expression of Cbf α -1 and ALP. Blockade of ERK1/2 phosphorylation in BMSCs by PD98059 suppressed osteogenic differentiation on chemical surfaces. These findings indicate a potential role for ERK in the osteogenic differentiation of BMSCs on surfaces modified by specific chemical functional groups, indicating that the microenvironment affects the differentiation of BMSCs. This observation has important implications for bone tissue engineering.
    08/2013; 2013(5411):361906. DOI:10.1155/2013/361906
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    • "Table 2 summarizes the main findings of the described studies. Phillips and co-authors analyzed [14] SAMs functionalized with four different functional groups, namely methyl (–CH 3 ,), hydroxyl (–OH), carboxyl (–COOH) and amino (–NH 2 ), and were able to demonstrate that the surface chemistry has an effect on the pattern of Fn adsorption, which in turn modulates the osteogenic differentiation of human MSCs (hMSCs). Differences in Fn conformation promoted different integrin–ligand interactions and the consequent activation of different intracellular signaling pathways [85]. "
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    ABSTRACT: Human mesenchymal stem cells (MSC) are currently recognized as a powerful cell source for regenerative medicine, notably for their capacity to differentiate into multiple cell types. The combination of MSC with biomaterials functionalized with instructive cues can be used as a strategy to direct specific lineage commitment, and thus improve the therapeutic efficacy of these cells. In terms of biomaterial design, one common approach is the functionalization of materials with ligands capable of directly binding to cell receptors and trigger specific differentiation signaling pathways. Other strategies focus on the use of moieties that have an indirect effect, acting for example as sequesters of bioactive ligands present in the extracellular milieu that will in turn interact with cells. Compared with complex biomolecules, the use of simple compounds such as chemical-moieties, peptides, and other small molecules can be advantageous by leading to less expensive and easily tunable biomaterial formulations. This review describes different strategies that have been used to promote substrate-mediated guidance of osteogenic differentiation of immature osteoblasts, osteoprogenitors and MSC, through chemically conjugated small moieties, both in 2D and 3D set-ups. In each case, the selected moiety the coupling strategy and the main findings of the study were highlighted. The latest advances and future perspectives in the field are also discussed.
    Acta biomaterialia 08/2013; 9(11). DOI:10.1016/j.actbio.2013.08.004 · 6.03 Impact Factor
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