scholarly journals Modulation of Hyaluronan Synthesis by the Interaction between Mesenchymal Stem Cells and Osteoarthritic Chondrocytes

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Eliane Antonioli ◽  
Carla A. Piccinato ◽  
Helena B. Nader ◽  
Moisés Cohen ◽  
Anna Carla Goldberg ◽  
...  

Bone marrow mesenchymal stem cells (BM-MSCs) are considered a good source for cellular therapy in cartilage repair. But, their potential to repair the extracellular matrix, in an osteoarthritic environment, is still controversial. In osteoarthritis (OA), anti-inflammatory action and extracellular matrix production are important steps for cartilage healing. This study examined the interaction of BM-MSC and OA-chondrocyte on the production of hyaluronan and inflammatory cytokines in a Transwell system. We compared cocultured BM-MSCs and OA-chondrocytes with the individually cultured controls (monocultures). There was a decrease in BM-MSCs cell count in coculture with OA-chondrocytes when compared to BM-MSCs alone. In monoculture, BM-MSCs produced higher amounts of hyaluronan than OA-chondrocytes and coculture of BM-MSCs with OA-chondrocytes increased hyaluronan production per cell. Hyaluronan synthase-1 mRNA expression was upregulated in BM-MSCs after coculture with OA-chondrocytes, whereas hyaluronidase-1 was downregulated. After coculture, lower IL-6 levels were detected in BM-MSCs compared with OA-chondrocytes. These results indicate that, in response to coculture with OA-chondrocytes, BM-MSCs change their behavior by increasing production of hyaluronan and decreasing inflammatory cytokines. Our results indicate that BM-MSCsper secould be a potential tool for OA regenerative therapy, exerting short-term effects on the local microenvironment even when cell:cell contact is not occurring.

2013 ◽  
Vol 378 ◽  
pp. 235-238 ◽  
Author(s):  
Jun Qiu ◽  
Zhuo Zhuang ◽  
Bo Huo

The mechanical stimulation from extracellular matrix could regulate physiological behavior of cells through the mechanism of mechanotransduction. Previous researches had shown that apoptosis could be regulated by the size of the cell adhesion area.However, the regulation of cell apoptosis by different adhesion shape with the same area is still unclear. This workfocused on the regulation of apoptosis for bone marrow mesenchymal stem cells (MSCs) by different circularity and area of adhesion geometry. We manufactured micro-pattern surface which was suitable for adhesion of MSCs by the technique of micro-contact printing. Three typesof geometry for individual is land of micro-pattern were designed. We adopted terminal-deoxynucleoitidyl transfer as emediated nick end labeling (TUNEL) method to detectcell apoptosis. This research shows that the adhesion geometry which has smaller area and greater circularity will promote apoptosis of MSCs. This indicates that MSCsmay prefer to live on the surface without any restrict. Ourstudies focused on the significantly important problem about interaction between extracellular matrix and physiological behavior of mesenchymal stem cells.


2015 ◽  
Vol 63 (5) ◽  
pp. 377-384 ◽  
Author(s):  
Marta Pokrywczynska ◽  
Marzena Anna Lewandowska ◽  
Sandra Krzyzanowska ◽  
Arkadiusz Jundzill ◽  
Marta Rasmus ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Hongliang He ◽  
Xiaozhen Liu ◽  
Liang Peng ◽  
Zhiliang Gao ◽  
Yun Ye ◽  
...  

Interactions between stem cells and extracellular matrix (ECM) are requisite for inducing lineage-specific differentiation and maintaining biological functions of mesenchymal stem cells by providing a composite set of chemical and structural signals. Here we investigated if cell-deposited ECM mimickedin vivoliver's stem cell microenvironment and facilitated hepatogenic maturation. Decellularization process preserved the fibrillar microstructure and a mix of matrix proteins in cell-deposited ECM, such as type I collagen, type III collagen, fibronectin, and laminin that were identical to those found in native liver. Compared with the cells on tissue culture polystyrene (TCPS), bone marrow mesenchymal stem cells (BM-MSCs) cultured on cell-deposited ECM showed a spindle-like shape, a robust proliferative capacity, and a suppressed level of intracellular reactive oxygen species, accompanied with upregulation of two superoxide dismutases. Hepatocyte-like cells differentiated from BM-MSCs on ECM were determined with a more intensive staining of glycogen storage, an elevated level of urea biosynthesis, and higher expressions of hepatocyte-specific genes in contrast to those on TCPS. These results demonstrate that cell-deposited ECM can be an effective method to facilitate hepatic maturation of BM-MSCs and promote stem-cell-based liver regenerative medicine.


2021 ◽  
Vol 2021 ◽  
pp. 1-26
Author(s):  
Honggang Xu ◽  
Bin Xu

Background. In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and noncoding RNAs in exosomes may play a major role. Aim. The present study is aimed at exploring the effect and mechanism of miR-326 in exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) on pyroptosis of cartilage and OA improvement. Methods. Exosomes from BMSCs (BMSC-Exos) were isolated and identified to incubate with OA chondrocytes. Proliferation, migration, specific gene and miR-326 expression, and pyroptosis of chondrocytes were detected. BMSCs or chondrocytes were transfected with miR-326 mimics or inhibitors to investigate the effect of miR-326 in BMSC-Exos on pyroptosis of chondrocytes and the potential mechanism. Finally, a rat OA model was established to verify the effect and mechanism of miR-326 in BMSC-Exos on cartilage of pyroptosis. Results. Incubation with BMSC-Exos could significantly improve the survival rate, migration ability, and chondrocyte-specific genes (COL2A1, SOX9, Agg, and Prg4) and miR-326 expression of OA chondrocytes and significantly inhibit pyroptosis of chondrocytes by downregulation of the levels of inflammatory cytokines, Caspase-1 activity, and pyroptosis-related proteins such as GSDMD, NLRP3, ASC, IL-1β, and IL-18 ( P < 0.01 ). PKH26 labeling confirmed the uptake of BMSC-Exos by chondrocytes. Incubation with exosomes extracted from BMSCs overexpressing miR-326 can significantly repress the pyroptosis of chondrocytes, while knockdown of miR-326 had the opposite effect ( P < 0.01 ). The same result was also demonstrated by direct interference with the expression level of miR-326 in chondrocytes ( P < 0.01 ). In addition, we found that the overexpression of miR-326 significantly inhibited the expression of HDAC3 and NF-κB p65 and significantly promoted the expression of STAT1, acetylated STAT1, and acetylated NF-κB p65 in chondrocytes ( P < 0.01 ). The targeted relationship between miR-326 and HDAC3 was verified by dual-luciferase reporter assay. Animal experiments confirmed the mechanism by which miR-326 delivered by BMSC-Exos inhibits pyroptosis of cartilage by targeting HDAC3 and STAT1/NF-κB p65 signaling pathway. Conclusion. BMSC-Exos can deliver miR-326 to chondrocytes and cartilage and improve OA by targeting HDAC3 and STAT1//NF-κB p65 to inhibit pyroptosis of chondrocytes and cartilage. Our findings provide a new mechanism for BMSC-Exos to treat OA.


Author(s):  
Li Wu ◽  
Dan Han ◽  
Jie Jiang ◽  
Xiaojie Xie ◽  
Xunran Zhao ◽  
...  

After the facial nerve axotomy (FNA), the distal end of the axon would gradually decay and disappear. Accumulated evidence shows that transplantation of bone marrow mesenchymal stem cells (BMSCs) reveals potential in the treatment of nervous system diseases or injuries. This study is aimed at investigating the therapeutic effects of co-transplantation of BMSCs and monocytes in FNA. We found that co-culture significantly elevated the CD4+/CD8+ ratio and CD4+ CD25+ T cell proportion compared with monocytes transplantation, and enhanced the differentiation of BMSCs into neurons. After the cell transplantation, the lowest apoptosis in the facial nerve nucleus was found in the co-transplantation group 2 (BMSCs:monocytes= 1:30). Moreover, the lowest expression levels of pro-inflammatory cytokines and the highest expression levels of anti-inflammatory cytokines were observed in the co-transplantation group 2 (BMSCs: monocytes= 1:30). The highest expression levels of protein in the JAK/STAT6 pathway and the SDF-1/CXCR4 axis were found in the co-transplantation group 2. BMSC/monocyte co-transplantation significantly improves the microenvironment in the facial nerve nucleus in FNA rats; therefore these findings suggest that it could promote the anti-/pro-inflammatory balance shift towards the anti-inflammatory microenvironment, alleviating survival conditions for BMSCs, regulating BMSC the chemotaxis homing, differentiation, and the section of BMSCs, and finally reducing the neuronal apoptosis. These findings might provide essential evidence for the in-hospital treatment of FNA with co-transplantation of BMSCs and monocytes.


2009 ◽  
Vol 73 (10) ◽  
pp. 2226-2233 ◽  
Author(s):  
Shi-Wu DONG ◽  
Da-Jun YING ◽  
Xiao-Jun DUAN ◽  
Zhao XIE ◽  
Zi-Jiang YU ◽  
...  

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