Hyaluronan substratum holds mesenchymal stem cells in slow-cycling mode by prolonging G1 phase

Liu, Chi-Mou; Yu, Chen-Hsiang; Chang, Cheng-Yen; Hsu, Chao Chin; Huang, Lynn Ling-Huei

doi:10.1007/s00441-008-0699-0

Cited by 25 publications

(22 citation statements)

References 29 publications

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“…Our evaluation of the effect of HA concentrations on MSCs indicates that HA affected MSC proliferation in a dose-dependent manner. Data in the literature shows that the addition of small concentrations of low molecular weight HA stimulates MSC proliferation [42,43], while the same concentration of high molecular weight HA appears to inhibit the cells [44,45]. Our experiments with high molecular weight HA in a 2D system did not show any significant effect on MSC proliferation (data not shown) while cells cultured on a calcite scaffold in a 3D system in the presence of HA of various concentrations displayed a reduction in cell number.…”

Section: Effect Of Ha Concentration On Msc Proliferationmentioning

confidence: 43%

Calcite Biohybrids as Microenvironment for Stem Cells

2012

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Abstract:A new type of composite 3D biomaterial that provides extracellular cues that govern the differentiation processes of mesenchymal stem cells (MSCs) has been developed. In the present study, we evaluated the chondrogenecity of a biohybrid composed of a calcium carbonate scaffold in its calcite polymorph and hyaluronic acid (HA). The source of the calcite scaffolding is an exoskeleton of a sea barnacle Tetraclita rifotincta (T. rifotincta), Pilsbry (1916). The combination of a calcium carbonate-based bioactive scaffold with a natural polymeric hydrogel is designed to mimic the organic-mineral composite of developing bone by providing a fine-tuned microenvironment. The results indicate that the calcite-HA interface creates a suitable microenvironment for the chondrogenic differentiation of MSCs, and therefore, the biohybrid may provide a tool for tissue-engineered cartilage.

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Section: Effect Of Ha Concentration On Msc Proliferationmentioning

confidence: 43%

Calcite Biohybrids as Microenvironment for Stem Cells

2012

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“…When we cultured PDMSCs on substrata containing more than 3 μg/cm 2 hyaluronan, their adherence rates were reduced (Liu et al 2008), either because of the antiadhesive property of hyaluronan (Pavesio et al 1997) or because of a lack of hyaluronan receptors on the membrane. Previous studies have reported that CD44 overexpression induced a dramatic increase in hyaluronan-mediated cell adhesion (Zhu and Bourguignon 1996) and increased hyaluronan-binding avidity (Lesley et al 2000).…”

Section: Discussionmentioning

confidence: 97%

“…Because PDMSCs grown on a hyaluronan-coated surface are slow cycling (Liu et al 2008), even when seeding density is doubled and tripled (Fig. 3), and proliferate less than cells grown on a polystyrene surface, they are able to resist doxorubicin.…”

Section: Discussionmentioning

confidence: 98%

Hyaluronan substratum induces multidrug resistance in human mesenchymal stem cells via CD44 signaling

Liu

Chang

et al. 2009

Cell Tissue Res

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Little information is available concerning multidrug resistance (MDR) in mesenchymal stem cells, although several studies have reported that MDR is associated with hyaluronan in neoplastic cells. We have evaluated whether a hyaluronan-coated surface modulates MDR in placenta-derived human mesenchymal stem cells (PDMSCs). We have found that PDMSCs cultured on a tissue-culture polystyrene surface coated with 30 microg/cm(2) hyaluronan are more resistant than control PDMSCs to doxorubicin. Inhibiting PI3K/Akt signaling has shown that the PI3K/Akt pathway modulates both P-glycoprotein activity and doxorubicin resistance. In addition, 10 microM verapamil dramatically suppresses the doxorubicin resistance induced by the hyaluronan-coated surface, indicating that P-glycoprotein activity is necessary for MDR. We have further found that PDMSCs treated with CD44 small interfering RNA (siRNA) and grown on a polystyrene surface coated with 30 microg/cm(2) hyaluronan have fewer P-glycoprotein(+) cells and lower CD44 expression levels (less than 60% in both cases) than PDMSCs not treated with CD44 siRNA and grown on the hyaluronan-coated surface. Moreover, treatment with CD44 siRNA suppresses the hyaluronan-substratum-induced doxorubicin resistance. We conclude that a hyaluronan substratum induces MDR in PDMSCs through CD44 signaling.

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“…The identification of hyaluronan in many locations where stem cells are present raised the possibility that hyaluronan influences these potent cells. Indeed, emerging studies [4–6] have proven the veracity of this hypothesis, and hyaluronan is now being studied as a key component that may be manipulated to induce desired stem cell behaviors.…”

Section: Hyaluronan Propertiesmentioning

confidence: 99%

Hyaluronan Regulates Cell Behavior: A Potential Niche Matrix for Stem Cells

Solís

Chen

Wong

et al. 2012

Biochemistry Research International

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Hyaluronan is a linear glycosaminoglycan that has received special attention in the last few decades due to its extraordinary physiological functions. This highly viscous polysaccharide is not only a lubricator, but also a significant regulator of cellular behaviors during embryogenesis, morphogenesis, migration, proliferation, and drug resistance in many cell types, including stem cells. Most hyaluronan functions require binding to its cellular receptors CD44, LYVE-1, HARE, layilin, and RHAMM. After binding, proteins are recruited and messages are sent to alter cellular activities. When low concentrations of hyaluronan are applied to stem cells, the proliferative activity is enhanced. However, at high concentrations, stem cells acquire a dormant state and induce a multidrug resistance phenotype. Due to the influence of hyaluronan on cells and tissue morphogenesis, with regards to cardiogenesis, chondrogenesis, osteogenesis, and neurogenesis, it is now been utilized as a biomaterial for tissue regeneration. This paper summarizes the most important and recent findings regarding the regulation of hyaluronan in cells.

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Hyaluronan substratum holds mesenchymal stem cells in slow-cycling mode by prolonging G1 phase

Cited by 25 publications

References 29 publications

Calcite Biohybrids as Microenvironment for Stem Cells

Calcite Biohybrids as Microenvironment for Stem Cells

Hyaluronan substratum induces multidrug resistance in human mesenchymal stem cells via CD44 signaling

Hyaluronan Regulates Cell Behavior: A Potential Niche Matrix for Stem Cells

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