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

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Mairim Alexandra Solis ◽  
Ying-Hui Chen ◽  
Tzyy Yue Wong ◽  
Vanessa Zaiatz Bittencourt ◽  
Yen-Cheng Lin ◽  
...  

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.

2014 ◽  
Vol 42 (3) ◽  
pp. 689-695 ◽  
Author(s):  
Rebecca J. Holley ◽  
Kate A. Meade ◽  
Catherine L.R. Merry

Differentiation and subsequent specialization of every cell within an organism is an intricate interwoven process. A complex network of signalling pathways eventually leads to the specification of a multitude of different cell types able to function co-operatively. HS (heparan sulfate) is a highly sulfated linear polysaccharide that resides at the pericellular cell–matrix interface where it dictates the binding and activity of a large number of proteins, including growth factors and morphogens such as members of the FGF (fibroblast growth factor) and BMP (bone morphogenetic protein) families. Embryonic stem cells derived from mice with mutations in components of the HS biosynthetic pathway provide an opportunity to dissect the contribution of HS to signalling pathways critical for regulating stem cell maintenance and differentiation. In addition to improving our understanding of signalling mechanisms, this knowledge enables the selection of exogenous HS saccharides to improve the efficiency and selectivity of directed differentiation protocols, offering a cost-effective alternative to high concentrations of expensive growth factors to drive differentiation towards a particular therapeutically relevant cell type.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Minkoo Seo ◽  
Jin-Chul Kim ◽  
Hyung-Ki Kim ◽  
Eun wook Choi ◽  
Suyeong Jeong ◽  
...  

Multipotent stem cells have the capacity to generate terminally differentiated cell types of each lineage; thus, they have great therapeutic potential for a wide variety of diseases. The most widely available stem cells are derived from human tissues, and their use for therapeutic application is limited by their high cost and low productivity. Herein, we report that conditioned media of mesenchymal stem cells (MSCs) isolated from deer antlers enhanced tissue regeneration through paracrine action via a combination of secreted growth factors and cytokines. Notably, DaMSC-conditioned media (DaMSC-CM) enhanced hair regeneration by activating the Wnt signaling pathway. In addition, DaMSC-CM had regenerative potential in damaged skin tissue through induction of skin regeneration-related genes. Remarkably, we identified round vesicles derived from DaMSC-CM, with an average diameter of ~120 nm that were associated with hair follicle formation, suggesting that secretory vesicles may act as paracrine mediators for modulation of local cellular responses. In addition, these secretory vesicles could regulate the expression of Wnt-3a, Wnt-10b, and lymphoid enhancer-binding factor-1 (LEF-1), which are related to tissue renewal. Thus, our findings demonstrate that the use of DaMSC-CM as a unique natural model for rapid and complete tissue regeneration has possible application for therapeutic development.


2020 ◽  
Vol 21 (11) ◽  
pp. 3924 ◽  
Author(s):  
Jessica Hedderich ◽  
Karima El Bagdadi ◽  
Peter Angele ◽  
Susanne Grässel ◽  
Andrea Meurer ◽  
...  

Bone marrow-derived mesenchymal stem cells (BMSCs) represent an alternative to chondrocytes to support cartilage regeneration in osteoarthritis (OA). The sympathetic neurotransmitter norepinephrine (NE) has been shown to inhibit their chondrogenic potential; however, their proliferation capacity under NE influence has not been studied yet. Therefore, we used BMSCs obtained from trauma and OA donors and compared the expression of adrenergic receptors (AR). Then, BMSCs from both donor groups were treated with NE, as well as with combinations of NE and α1-, α2- or β1/2-AR antagonists (doxazosin, yohimbine or propranolol). Activation of AR-coupled signaling was investigated by analyzing ERK1/2 and protein kinase A (PKA) phosphorylation. A similar but not identical subset of ARs was expressed in trauma (α2B-, α2C- and β2-AR) and OA BMSCs (α2A-, α2B-, and β2-AR). NE in high concentrations inhibited the proliferation of both trauma and OA BMCSs significantly. NE in low concentrations did not influence proliferation. ERK1/2 as well as PKA were activated after NE treatment in both BMSC types. These effects were abolished only by propranolol. Our results demonstrate that NE inhibits the proliferation and accordingly lowers the regenerative capacity of human BMSCs likely via β2-AR-mediated ERK1/2 and PKA phosphorylation. Therefore, targeting β2-AR-signaling might provide novel OA therapeutic options.


2019 ◽  
Vol 20 (2) ◽  
pp. 385 ◽  
Author(s):  
Fabiana Mammoli ◽  
Sara Castiglioni ◽  
Sandra Parenti ◽  
Concettina Cappadone ◽  
Giovanna Farruggia ◽  
...  

Magnesium (Mg) is crucial for bone health. Low concentrations of Mg inhibit the activity of osteoblasts while promoting that of osteoclasts, with the final result of inducing osteopenia. Conversely, little is known about the effects of high concentrations of extracellular Mg on osteoclasts and osteoblasts. Since the differentiation and activation of these cells is coordinated by vitamin D3 (VD3), we investigated the effects of high extracellular Mg, as well as its impact on VD3 activity, in these cells. U937 cells were induced to osteoclastic differentiation by VD3 in the presence of supra-physiological concentrations (>1 mM) of extracellular Mg. The effect of high Mg concentrations was also studied in human bone-marrow-derived mesenchymal stem cells (bMSCs) induced to differentiate into osteoblasts by VD3. We demonstrate that high extra-cellular Mg levels potentiate VD3-induced osteoclastic differentiation, while decreasing osteoblastogenesis. We hypothesize that Mg might reprogram VD3 activity on bone remodeling, causing an unbalanced activation of osteoclasts and osteoblasts.


APOPTOSIS ◽  
2012 ◽  
Vol 17 (9) ◽  
pp. 964-974 ◽  
Author(s):  
Fulvia Zanichelli ◽  
Stefania Capasso ◽  
Giovanni Di Bernardo ◽  
Marilena Cipollaro ◽  
Eleonora Pagnotta ◽  
...  

Nanoscale ◽  
2017 ◽  
Vol 9 (28) ◽  
pp. 9848-9858 ◽  
Author(s):  
Maria del Mar Encabo-Berzosa ◽  
Maria Sancho-Albero ◽  
Alejandra Crespo ◽  
Vanesa Andreu ◽  
Victor Sebastian ◽  
...  

Mesenchymal stem cells (MSCs) not only can be differentiated into different cell types but also have tropism towards injured or inflamed tissues serving as repair cells.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xinyu Gao ◽  
Jin Zhou ◽  
Jinghua Wang ◽  
Xiushuai Dong ◽  
Yuying Chang ◽  
...  

Abstract Objective This study was to explore the effect of exosomal miR-155 derived from bone marrow mesenchymal stem cells (BMSCs) on stemness maintenance and drug resistance in MPC-11 multiple myeloma cells. Methods MPC-11 cells were transfected with mimics or inhibitors of miR-155. miR-155 expression was detected by qRT-PCR, cell condition was observed, and the expression of stemness maintenance markers OCT-4 and Nanog was observed by immunofluorescence. The expression of proteins associated with the Hedgehog signaling pathway and drug resistance was evaluated by western blot. To investigate whether exosomes affect cell behavior by horizontal delivery of miR-155, MPC-11 cells were co-cultured with exosomes isolated from BMSCs that were transfected with mimics or inhibitors of miR-155. Cell proliferation and the expression of proteins related to stemness maintenance protein and drug resistance were examined. Results In function assays, after miR-155-mimics transfection, the expression levels of proteins related to stemness maintenance marker, Hedgehog signaling, and drug resistance were increased in MPC-11 cells. BMSC-derived exosomes carrying miR-155 inhibited apoptosis, promoted cell division, and upregulated the expression of protein associated with stemness maintenance, Hedgehog signaling, and drug resistance. Conclusion Therefore, our findings indicate that exosomal delivery of miR-155 exerted the same effect as transfection did on the stemness maintenance and drug resistance of multiple myeloma cells.


2016 ◽  
Vol 12 ◽  
pp. 38-47 ◽  
Author(s):  
Aleksandra Skubis ◽  
Bartosz Sikora ◽  
Nikola Zmarzły ◽  
Emilia Wojdas ◽  
Urszula Mazurek

This review article provides an overview on adipose-derived stem cells (ADSCs) for implications in bone tissue regeneration. Firstly this article focuses on mesenchymal stem cells (MSCs) which are object of interest in regenerative medicine. Stem cells have unlimited potential for self-renewal and develop into various cell types. They are used for many therapies such as bone tissue regeneration. Adipose tissue is one of the main sources of mesenchymal stem cells (MSCs). Regenerative medicine intends to differentiate ADSC along specific lineage pathways to effect repair of damaged or failing organs. For further clinical applications it is necessary to understand mechanisms involved in ADSCs proliferation and differentiation. Second part of manuscript based on osteogenesis differentiation of stem cells. Bones are highly regenerative organs but there are still many problems with therapy of large bone defects. Sometimes there is necessary to make a replacement or expansion new bone tissue. Stem cells might be a good solution for this especially ADSCs which manage differentiate into osteoblast in in vitro and in vivo conditions.


2016 ◽  
Vol 14 (6) ◽  
pp. 1041-1046 ◽  
Author(s):  
Lina Xiong ◽  
He Yan ◽  
Lei Shi ◽  
Ziyao Mo

The purpose of this study was to investigate the susceptibility of waterborne strains of Legionella to eight antimicrobials commonly used in legionellosis therapy. The minimum inhibitory concentrations (MICs) of 66 environmental Legionella strains, isolated from fountains and cooling towers of public facilities (hotels, schools, and shopping malls) in Macau and Guangzhou, were tested using the microdilution method in buffered yeast extract broth. The MIC50/MIC90 values for erythromycin, cefotaxime (CTX), doxycycline (DOC), minocycline (MIN), azithromycin, ciprofloxacin, levofloxacin (LEV), and moxifloxacin were 0.125/0.5 mg/L, 4/8 mg/L, 8/16 mg/L, 4/8 mg/L, 0.125/0.5 mg/L, 0.031/0.031 mg/L, 0.031/0.031 mg/L, and 0.031/0.062 mg/L, respectively. Legionella isolates were inhibited by either low concentrations of macrolides and fluoroquinolones, or high concentrations of CTX and tetracycline drugs. LEV was the most effective drug against different Legionella species and serogroups of L. pneumophila isolates. The latter were inhibited in decreasing order by MIN > CTX >DOC, while non-L. pneumophila isolates were inhibited by CTX> MIN >DOC. In this study, we evaluated drug resistance of pathogenic bacteria from the environment. This may help predict the emergence of drug resistance, improve patient outcomes, and reduce hospitalization costs.


1999 ◽  
Vol 276 (1) ◽  
pp. L114-L121 ◽  
Author(s):  
S. E. Hall ◽  
S. Lim ◽  
I. R. Witherden ◽  
T. D. Tetley ◽  
P. J. Barnes ◽  
...  

Annexin I (lipocortin 1) is abundant in lung secretions. Concentrations rise after oral glucocorticoid, but the effect of inhaled budesonide on annexin I release is unknown. Extracellular annexin I in bronchoalveolar lavage fluid (BALF) from 11 asthmatic patients was unaffected by inhaled budesonide (800 μg twice daily for 4 wk; mean after budesonide, 110 ng/mg albumin; after placebo, 107 ng/mg albumin). Rat alveolar macrophages (AMs) and alveolar epithelial type II (ATII) cells were cultured alone and with budesonide or dexamethasone. Mean basal concentrations of cellular (3.5 ng/106 AMs; 4.4 ng/106 ATII cells) and secreted (1.4 ng/106 AMs; 1.8 ng/106 ATII cells) annexin I were similar in AMs and ATII cells. Although budesonide subdued annexin I secretion from both cell types, dexamethasone stimulated annexin I release. Annexin I release from ATII cells peaked at 10−7 M dexamethasone but at 10−3 M dexamethasone from AMs. Thus, at low concentrations of dexamethasone, ATII cells probably contribute more annexin I to respiratory tract secretions than AMs, although at high concentrations, both cells probably contribute. The study demonstrates previously undescribed differences between glucocorticoids and between AMs and ATII cells with respect to annexin I regulation.


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