Low molecular weight blue mussel hydrolysates inhibit adipogenesis in mouse mesenchymal stem cells through upregulating HO-1/Nrf2 pathway

2020 ◽  
Vol 136 ◽  
pp. 109603
Author(s):  
Yunok Oh ◽  
Chang-Bum Ahn ◽  
Jae-Young Je
Author(s):  
Vyacheslav Ogay ◽  
Miras Karzhauov ◽  
Ainur Mukhambetova ◽  
Eric Raimagambetov ◽  
Nurlan Batpenov

Introduction: The purpose of this study was to investigate whether intra-articular injection of synovium-derived mesenchymal stem cells (SD MSCs) with low molecular weight hyaluronic acid (HA) could promote regeneration of massive cartilage in rabbits.Material and methods: The SD MSCs were harvested from the knees of 10 Flemish giant rabbits, expanded in culture, and characterized. A reproducible 4-mm cylindrical defect was created in the intercondylar groove area using a kit for the mosaic chondroplasty of femoral condyle COR (De Puy, Mitek). The defect was made within the cartilage layer without destruction of subchondral bone. Two weeks after the cartilage defect, SD MSCs (2 × 106 cell/0.15 ml) were suspended in 0.5% low molecular weight HA (0.15 ml) and injected into the left knee, and HA solution (0.30 ml) alone was placed into the right knee. Cartilage regeneration in the experimental and control groups were evaluated by macroscopically and histologically at 10, 30, and 60 days.Results: On day 10, after intra-articular injection of SD MSCs, we observed an early process of cartilage regeneration in the defect area. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chodroblasts. In contrast, an injection of HA did not induce reparation of cartilage in the defect area. At 30 days, macroscopic observation showed that the size of cartilage defect after SD MSC injection was significantly smaller than after HA injection. Histological score was also better in the MSC- treated intercondylar defect. At 60 days after MSC treatment, cartilage defect was nearly nonexistent and looked similar to an intact cartilage.Conclusion: Thus, intra-articular injection of SD MSCs can adhere to the defect in the intercondylar area, and promote cartilage regeneration in rabbits.


RSC Advances ◽  
2016 ◽  
Vol 6 (35) ◽  
pp. 29365-29370 ◽  
Author(s):  
Jun-Ho Hyung ◽  
Chang-Bum Ahn ◽  
Jae-Young Je

Ark shell protein promotes bone formation through regulating osteoblast differentiation.


2016 ◽  
Vol 4 (20) ◽  
pp. 3504-3508 ◽  
Author(s):  
Yalong Hu ◽  
Wenxia Gao ◽  
Fang Wu ◽  
Huayue Wu ◽  
Bin He ◽  
...  

Four low molecular weight gels (LMWGs) with different moduli were fabricated as scaffolds to investigate the differentiation of mesenchymal stem cells (MSCs).


2019 ◽  
Vol 26 (10) ◽  
pp. 785-791
Author(s):  
Ji-Eun Kim ◽  
Hye-Jin Seo ◽  
SuJin Lee ◽  
Jun-Hyeog Jang

Background: Laminin, a member of the Extracellular Matrix (ECM), is a glycoprotein that is used as a factor that affects cell adhesion, proliferation, survival, and differentiation. Of these, five globular domains (LG domains) of the alpha chain play an important role in influencing the cell by binding to the integrin. Objective: This study aimed to evaluate the ability of globular domains 1-3 of laminin alpha2 (rhLAMA2LG1-3) in maintaining the pluripotency of human Mesenchymal Stem Cells (hMSCs), which are widely used in regenerative medicine. Methods: hMSCs were grown in the medium supplemented with rhLAMA2LG1-3, then the effect of the protein on hMSCs were confirmed through cell adhesion assay, proliferation assay and RTPCR. Results: rhLAMA2LG1-3 expressed in Escherichia coli has a molecular weight of 70 kDa, at 1 µg/ml concentration of rhLAMA2LG1-3, the attachment and proliferation of hMSCs were approximately 3.18-fold and 1.67-fold, respectively, more efficient than those of untreated controls. In addition, the undifferentiated state and degree of stemness of hMSCs were measured, on the basis of CD90 and CD105 levels. In the rhLAMA2LG1-3-treated hMSCs, the expression levels of CD90 and CD105 increased by 2.83-fold and 1.62-fold, respectively, compared to those in untreated controls. Conclusion: rhLAMA2LG1-3 can be potentially used in stem cell therapy to improve the viability and maintain the undifferentiated state of hMSCs.


2020 ◽  
Vol 6 (16) ◽  
pp. eaba1334 ◽  
Author(s):  
Jisun Lim ◽  
Jinbeom Heo ◽  
Hyein Ju ◽  
Ji-Woong Shin ◽  
YongHwan Kim ◽  
...  

Glutathione (GSH), the most abundant nonprotein thiol functioning as an antioxidant, plays critical roles in maintaining the core functions of mesenchymal stem cells (MSCs), which are used as a cellular immunotherapy for graft-versus-host disease (GVHD). However, the role of GSH dynamics in MSCs remains elusive. Genome-wide gene expression profiling and high-throughput live-cell imaging assays revealed that CREB1 enforced the GSH-recovering capacity (GRC) of MSCs through NRF2 by directly up-regulating NRF2 target genes responsible for GSH synthesis and redox cycling. MSCs with enhanced GSH levels and GRC mediated by CREB1-NRF2 have improved self-renewal, migratory, anti-inflammatory, and T cell suppression capacities. Administration of MSCs overexpressing CREB1-NRF2 target genes alleviated GVHD in a humanized mouse model, resulting in improved survival, decreased weight loss, and reduced histopathologic damages in GVHD target organs. Collectively, these findings demonstrate the molecular and functional importance of the CREB1-NRF2 pathway in maintaining MSC GSH dynamics, determining therapeutic outcomes for GVHD treatment.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Urszula Skalska ◽  
Ewa Kontny

Adiponectin and leptin have recently emerged as potential risk factors in rheumatoid arthritis (RA) pathogenesis. In this study we evaluated the effects of adiponectin and leptin on immunomodulatory function of adipose mesenchymal stem cells (ASCs) derived from infrapatellar fat pad of RA patients. ASCs were stimulated with leptin, low molecular weight (LMW) and high/middle molecular weight (HMW/MMW) adiponectin isoforms. The secretory activity of ASCs and their effect on rheumatoid synovial fibroblasts (RA-FLS) and peripheral blood mononuclear cells (PBMCs) from healthy donors have been analysed. RA-ASCs secreted spontaneously TGFβ, IL-6, IL-1Ra, PGE2, IL-8, and VEGF. Secretion of all these factors was considerably upregulated by HMW/MMW adiponectin, but not by LMW adiponectin and leptin. Stimulation with HMW/MMW adiponectin partially abolished proproliferative effect of ASC-derived soluble factors on RA-FLS but did not affect IL-6 secretion in FLS cultures. ASCs pretreated with HMW/MMW adiponectin maintained their anti-inflammatory function towards PBMCs, which was manifested by moderate PBMCs proliferation inhibition and IL-10 secretion induction. We have proved that HMW/MMW adiponectin stimulates secretory potential of rheumatoid ASCs but does not exert strong impact on ASCs function towards RA-FLS and PBMCs.


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