scholarly journals Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells

Author(s):  
Asim Cengiz Akbulut ◽  
Grzegorz B. Wasilewski ◽  
Nikolas Rapp ◽  
Francesco Forin ◽  
Heike Singer ◽  
...  

Development of clinical stem cell interventions are hampered by immature cell progeny under current protocols. Human mesenchymal stem cells (hMSCs) are characterized by their ability to self-renew and differentiate into multiple lineages. Generating hMSCs from pluripotent stem cells (iPSCs) is an attractive avenue for cost-efficient and scalable production of cellular material. In this study we generate mature osteoblasts from iPSCs using a stable expandable MSC intermediate, refining established protocols. We investigated the timeframe and phenotype of cells under osteogenic conditions as well as the effect of menaquinone-7 (MK-7) on differentiation. From day 2 we noted a significant increase in RUNX2 expression under osteogenic conditions with MK-7, as well as decreases in ROS species production, increased cellular migration and changes to dynamics of collagen deposition when compared to differentiated cells that were not treated with MK-7. At day 21 OsteoMK-7 increased alkaline phosphatase activity and collagen deposition, as well as downregulated RUNX2 expression, suggesting to a mature cellular phenotype. Throughout we note no changes to expression of osteocalcin suggesting a non-canonical function of MK-7 in osteoblast differentiation. Together our data provide further mechanistic insight between basic and clinical studies on extrahepatic activity of MK-7. Our findings show that MK-7 promotes osteoblast maturation thereby increasing osteogenic differentiation.

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1592
Author(s):  
Sevil Özer ◽  
H. Seda Vatansever ◽  
Feyzan Özdal-Kurt

Bone marrow mesenchymal stem cells (BM-MSCs) are used to repair hypoxic or ischemic tissue. After hypoxic the level of ATP is decreases, cellular functions do not continue and apoptosis or necrosis occur. Apoptosis is a progress of programmed cell death that occurs in normal or pathological conditions. In this study, we were investigated the hypoxic effect on apoptosis in mesenchymal stem cell. Bone marrow-derived stem cells were cultured in hypoxic (1% or 3%) or normoxic conditions 24, 96 well plates for 36 h. Cell viability was shown by MTT assay on 36 h. After fixation of cells with 4% paraformaldehyde, distributions of caspase-3, Bcl-2 and Bax with indirect immunoperoxidase technique, apoptotic cells with TUNEL assay were investigated. All staining results were evaluated using H-score analyses method with ANOVA, statistically. As a result, hypoxic condition was toxic for human mesenchymal stem cells and the number of death cell was higher in that than normoxic condition.


2015 ◽  
Vol 3 (16) ◽  
pp. 3150-3168 ◽  
Author(s):  
Sunil Kumar Boda ◽  
Greeshma Thrivikraman ◽  
Bikramjit Basu

Substrate magnetization as a tool for modulating the osteogenesis of human mesenchymal stem cells for bone tissue engineering applications.


2021 ◽  
Author(s):  
Pnina Green ◽  
Inna Kan ◽  
Ronit Mesilati-Stahy ◽  
Nurit Argov-Argaman ◽  
Daniel Offen

AbstractNeuronal membranes contain exceptionally high concentrations of long-chain polyunsaturated fatty acids (PUFA), docosahexaenoic acid (DHA) and arachidonic acid (ARA), which are essential for neuronal development and function. Adult bone-marrow-derived mesenchymal stem cells (MSC) can be induced to possess some neuronal characteristics. Here we examined the effects of neuronal induction on the PUFA metabolism specific pathways. Differentiated cells contained ~30% less ARA than MSC. The expression of specific ARA metabolizing enzymes was upregulated, notably that of prostaglandin E2 synthase which increased more than 15-fold, concomitantly with a 3-fold increase in the concentration of PGE2 in the medium. Moreover, induced differentiation was associated with enhanced incorporation of exogenous DHA, upregulation of acyl-CoA synthases, fatty acid binding proteins, choline kinase (CK) and phosphatidylserine synthases as well as increased total cellular phospholipids (PL). These findings suggest that active ARA metabolites may be important in the differentiation process and that neuronal induction prepares the resulting cells for increased DHA incorporation through the action of specific enzymes.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Seung-Cheol Lee ◽  
Yoo-Jung Lee ◽  
Min Kyoung Shin ◽  
Jung-Suk Sung

Human mesenchymal stem cells derived from adipose tissue (hADMSCs) are a desirable candidate in regenerative medicine. hADMSCs secrete growth factors, cytokines, and chemokines and also express various receptors that are important in cell activation, differentiation, and migration to injured tissue. We showed that the expression level of chemokine receptor CXCR6 was significantly increased by ~2.5-fold in adipogenic-differentiated cells (Ad), but not in osteogenic-differentiated cells (Os) when compared with hADMSCs. However, regulation of CXCR6 expression on hADMSCs by using lentiviral particles did not affect the differentiation potential of hADMSCs. Increased expression of CXCR6 on Ad was mediated by both receptor recycling, which was in turn regulated by secretion of CXCL16, and de novo synthesis. The level of soluble CXCL16 was highly increased in both Ad and Os in particular, which inversely correlates with the expression on a transmembrane-bound form of CXCL16 that is cleaved by disintegrin and metalloproteinase. We concluded that the expression of CXCR6 is regulated by receptor degradation or recycling when it is internalized by interaction with CXCL16 and by de novo synthesis of CXCR6. Overall, our study may provide an insight into the molecular mechanisms of the CXCR6 reciprocally expressed on differentiated cells from hADMSCs.


2020 ◽  
Vol 56 (20) ◽  
pp. 3043-3046 ◽  
Author(s):  
Swati Sharma ◽  
Chirag Kulkarni ◽  
Manish M. Kulkarni ◽  
Rafat Ali ◽  
Konica Porwal ◽  
...  

We demonstrate the ability of two tripeptides to promote proliferation and modulate the mechanical properties of human mesenchymal stem cells (hMSCs).


2019 ◽  
Vol 55 (6) ◽  
pp. 1029-1040 ◽  
Author(s):  
Xiuxiu Yin ◽  
Linping Hu ◽  
Yawen Zhang ◽  
Caiying Zhu ◽  
Hui Cheng ◽  
...  

AbstractThe bone marrow (BM) niche regulates multiple hematopoietic stem cell (HSC) processes. Clinical treatment for hematological malignancies by HSC transplantation often requires preconditioning via total body irradiation, which severely and irreversibly impairs the BM niche and HSC regeneration. Novel strategies are needed to enhance HSC regeneration in irradiated BM. We compared the effects of EGF, FGF2, and PDGFB on HSC regeneration using human mesenchymal stem cells (MSCs) that were transduced with these factors via lentiviral vectors. Among the above niche factors tested, MSCs transduced with PDGFB (PDGFB-MSCs) most significantly improved human HSC engraftment in immunodeficient mice. PDGFB-MSC-treated BM enhanced transplanted human HSC self-renewal in secondary transplantations more efficiently than GFP-transduced MSCs (GFP-MSCs). Gene set enrichment analysis showed increased antiapoptotic signaling in PDGFB-MSCs compared with GFP-MSCs. PDGFB-MSCs exhibited enhanced survival and expansion after transplantation, resulting in an enlarged humanized niche cell pool that provide a better humanized microenvironment to facilitate superior engraftment and proliferation of human hematopoietic cells. Our studies demonstrate the efficacy of PDGFB-MSCs in supporting human HSC engraftment.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sung Keun Kang ◽  
Il Seob Shin ◽  
Myung Soon Ko ◽  
Jung Youn Jo ◽  
Jeong Chan Ra

Human mesenchymal stem cells (MSCs) communicate with other cells in the human body and appear to “home” to areas of injury in response to signals of cellular damage, known as homing signals. This review of the state of current research on homing of MSCs suggests that favorable cellular conditions and thein vivoenvironment facilitate and are required for the migration of MSCs to the site of insult or injuryin vivo. We review the current understanding of MSC migration and discuss strategies for enhancing both the environmental and cellular conditions that give rise to effective homing of MSCs. This may allow MSCs to quickly find and migrate to injured tissues, where they may best exert clinical benefits resulting from improved homing and the presence of increased numbers of MSCs.


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