Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

Chen, Po Yang; Huang, Lynn Ling-Huei; Hsieh, Hsyue Jen

doi:10.1016/j.bbrc.2007.04.211

Cited by 53 publications

(43 citation statements)

References 21 publications

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“…Therefore, holding stem cells in vitro in slow-cycling mode by decelerating their rate of proliferation is an appropriate strategy for keeping them in a primitive state. Our previous findings (Chen et al 2007) indicated that hyaluronan is useful for preserving the differentiation potential of longterm cultured murine adipose-derived stromal cells. Our present findings provide further evidence that PDMSCs grown on a hyaluronan-coated surface are maintained in slow-cycling mode, and that the prolonged G 1 phase is the main cause of reduced proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous finding (Chen et al 2007) suggests that hyaluronan is also important in mesenchymal stem cells because it preserves the differentiation potential of long-term cultured murine adipose-derived stromal cells. Moreover, several studies have reported that hyaluronan suppresses the proliferation of mesenchymal cells, including synovial cells, 3T3 cells (Goldberg and Toole 1987), smooth muscle cells (Cuff et al 2001), and fibroblasts (Croce et al 2003).…”

Section: Introductionmentioning

confidence: 98%

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

Liu

Chang

et al. 2008

Cell Tissue Res

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We examined, in vitro, whether hyaluronan induces slow cycling in placenta-derived mesenchymal stem cells (PDMSCs) by comparing cell growth on a hyaluronan-coated surface with cell growth on a tissue-culture polystyrene surface. The hyaluronan-coated surface significantly downregulated the proliferation of PDMSCs, more of which were maintained in the G(0)/G(1) phases than were cells on the tissue-culture polystyrene surface. Both PKH-26 labeling and BrdU incorporation assays showed that most PDMSCs grown on a hyaluronan-coated surface duplicated during cultivation indicating that the hyaluronan-coated surface did not inhibit PDMSCs from entering the cell cycle. Mitotic synchronization showed that the G(1)-phase transit was prolonged in PDMSCs growing on a hyaluronan-coated surface. Increases in p27(Kip1) and p130 were the crucial factors that allowed hyaluronan to lengthen the G(1) phase. Thus, hyaluronan might be a promising candidate for maintaining stem cells in slow-cycling mode by prolonging their G(1)-phase transit.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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

Liu

Chang

et al. 2008

Cell Tissue Res

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“…Interestingly, hyaluronan also inhibits the differentiation of adiposederived stromal cells, osteoblasts, and keratinocytes (16)(17)(18)(19). Although hyaluronan requires TLR2 or TLR4 to activate dendritic cells, macrophages, and microglia (6)(7)(8)(9), it is unclear whether hyaluronan also requires TLRs to modulate differentiation.…”

mentioning

confidence: 99%

Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2

Sloane

Batt

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

299

301

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Failure of remyelination is largely responsible for sustained neurologic symptoms in multiple sclerosis (MS). MS lesions contain hyaluronan deposits that inhibit oligodendrocyte precursor cell (OPC) maturation. However, the mechanism behind this inhibition is unclear. We report here that Toll-like receptor 2 (TLR2) is expressed by oligodendrocytes and is up-regulated in MS lesions. Pathogenderived TLR2 agonists, but not agonists for other TLRs, inhibit OPC maturation in vitro. Hyaluronan-mediated inhibition of OPC maturation requires TLR2 and MyD88, a TLR2 adaptor molecule. Ablated expression of TLR2 also enhances remyelination in a lysolecithin animal model. Hyaluronidases expressed by OPCs degrade hyaluronan to hyaluronan oligomers, a requirement for hyaluronan/TLR2 signaling. MS lesions contain both TLR2 + oligodendrocytes and lowmolecular-weight hyaluronan, consistent with their importance to remyelination in MS. We thus have defined a mechanism controlling remyelination failure in MS where hyaluronan is degraded by hyaluronidases into hyaluronan oligomers that block OPC maturation and remyelination through TLR2-MyD88 signaling.hyaluronidase | MyD88 | innate immunity I n multiple sclerosis (MS), destruction of CNS myelin accounts for a majority of neurologic symptoms. MS patients typically exhibit a relapsing/remitting course in which relapses result from inflammation and demyelination and remissions result from resolution of inflammation and remyelination. Secondary progressive MS, which typically begins in patients after a decade of relapsing/ remitting MS, exhibits irreversible neurologic disability.Most chronic MS lesions show little if any remyelination. The failure of remyelination in MS theoretically could be the consequence of a deficiency in the number of oligodendrocyte progenitor cells (OPCs), absence of a promyelination signal, or the presence of inhibitory influences on OPCs. It therefore is of interest that the histopathology of the MS lesion has revealed the presence of OPCs and premyelinating oligodendrocytes in chronic MS lesions. The premyelinating oligodendrocytes extend processes that contact but fail to myelinate axons (1-4), thus suggesting failure of remyelination is caused by the loss of promyelination signals or the presence of inhibitory signals.Recently, the glycosaminoglycan hyaluronan was identified within MS lesions and found to inhibit OPC maturation and remyelination in an MS animal model (5). The mechanism underlying this inhibition is unknown. Because hyaluronan can function as an endogenous mammalian ligand for Toll-like receptors (TLRs) 2 and 4 in innate immune cell activation (6-9), we reasoned that TLR stimulation also may be required for hyaluronan-mediated blocking of OPC maturation.Although TLRs and the Drosophila ortholog Toll have welldescribed functions in innate immune cells (6-12), TLRs also have potent functions outside the immune system. Toll and TLR have diverse roles in axonal pathfinding, dorsoventral patterning, and cell-fate determination (13). In particul...

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“…First, we found that, while SVF cells in NM appeared senescent at early stages, as described in previous studies [28], the Lin -cells proliferated for much longer before they showed signs of aging. Jiang et al reported a type of modified LSM, which was able to maintain longer-term proliferation of mouse BMSCs in vitro [22].…”

mentioning

confidence: 57%

The Adipose-Derived Lineage-Negative Cells Are Enriched Mesenchymal Stem Cells and Promote Limb Ischemia Recovery in Mice

Qin

Zhou

et al. 2014

Stem Cells and Development

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White adipose tissue (WAT) is a very attractive source of mesenchymal stem cells (MSCs) because of its availability and ease of harvest. However, the current method of isolating adipose tissue-derived MSCs often relies on the adhesiveness of the cultured stromal-vascular fraction (SVF). Unfortunately, the SVF is a heterogeneous cell population containing many cell types, including adipocyte precursor cells, endothelial cells, pericytes, multipotent MSCs, erythrocytes, and hematopoietic cells. Here we systematically characterized the adipose tissue-derived lineage-negative (Lin(-)) cell population using various surface markers and a set of cell proliferation and differentiation assays. We demonstrate clearly that the Lin(-) cell population represents enriched MSCs, which were identified by their high expression of MSC surface markers, and that these cells are a robust population with a vigorous growth capability and delayed aging. This cell population also demonstrated a much higher capacity for differentiation into osteogenic, chondrogenic and adipogenic cell lineages related to MSCs than did the SVF. These cells promoted recovery from limb ischemia, likely via production of vascular endothelial growth factor, an angiogenic factor. Our study demonstrates that Lin(-) cells are enriched in MSCs and provides a reliable method for isolating purer MSCs than SVF cells from the WAT, especially for obtaining fresh MSCs for clinical applications. In summary, this study identified a new, reliable method for enrichment of WAT MSCs with regenerative repairing features.

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Hyaluronan preserves the proliferation and differentiation potentials of long-term cultured murine adipose-derived stromal cells

Cited by 53 publications

References 21 publications

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

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

Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2

The Adipose-Derived Lineage-Negative Cells Are Enriched Mesenchymal Stem Cells and Promote Limb Ischemia Recovery in Mice

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