scholarly journals Cholesterol-Dependent Modulation of Stem Cell Biomechanics: Application to Adipogenesis

2019 ◽  
Vol 141 (8) ◽  
Author(s):  
Shan Sun ◽  
Djanybek Adyshev ◽  
Steven Dudek ◽  
Amit Paul ◽  
Andrew McColloch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Young’S Modulus ◽  
Cell Mechanics ◽  
Young's Modulus ◽  
Adipogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Cell Stiffness ◽  
Cholesterol Depletion

Cell mechanics has been shown to regulate stem cell differentiation. We have previously reported that altered cell stiffness of mesenchymal stem cells can delay or facilitate biochemically directed differentiation. One of the factors that can affect the cell stiffness is cholesterol. However, the effect of cholesterol on differentiation of human mesenchymal stem cells remains elusive. In this paper, we demonstrate that cholesterol is involved in the modulation of the cell stiffness and subsequent adipogenic differentiation. Rapid cytoskeletal actin reorganization was evident and correlated with the cell's Young's modulus measured using atomic force microscopy. In addition, the level of membrane-bound cholesterol was found to increase during adipogenic differentiation and inversely varied with the cell stiffness. Furthermore, cholesterol played a key role in the regulation of the cell morphology and biomechanics, suggesting its crucial involvement in mechanotransduction. To better understand the underlying mechanisms, we investigated the effect of cholesterol on the membrane–cytoskeleton linker proteins (ezrin and moesin). Cholesterol depletion was found to upregulate the ezrin expression which promoted cell spreading, increased Young's modulus, and hindered adipogenesis. In contrast, cholesterol enrichment increased the moesin expression, decreased Young's modulus, and induced cell rounding and facilitated adipogenesis. Taken together, cholesterol appears to regulate the stem cell mechanics and adipogenesis through the membrane-associated linker proteins.

scholarly journals Emerging Potential of Exosomes on Adipogenic Differentiation of Mesenchymal Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuxuan Zhong ◽  
Xiang Li ◽  
Fanglin Wang ◽  
Shoushuai Wang ◽  
Xiaohong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Adipogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Cartilage Tissue ◽  
Differentiation Potential ◽  
Engineering Research ◽  
Adipose Tissue Engineering

The mesenchymal stem cells have multidirectional differentiation potential and can differentiate into adipocytes, osteoblasts, cartilage tissue, muscle cells and so on. The adipogenic differentiation of mesenchymal stem cells is of great significance for the construction of tissue-engineered fat and the treatment of soft tissue defects. Exosomes are nanoscale vesicles secreted by cells and widely exist in body fluids. They are mainly involved in cell communication processes and transferring cargo contents to recipient cells. In addition, exosomes can also promote tissue and organ regeneration. Recent studies have shown that various exosomes can influence the adipogenic differentiation of stem cells. In this review, the effects of exosomes on stem cell differentiation, especially on adipogenic differentiation, will be discussed, and the mechanisms and conclusions will be drawn. The main purpose of studying the role of these exosomes is to understand more comprehensively the influencing factors existing in the process of stem cell differentiation into adipocytes and provide a new idea in adipose tissue engineering research.

scholarly journals Osteogenic differentiation of follicular stem cells on nano-Saghez scaffold containing BMP2

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Hananeh Bayat ◽  
Hassan Shahabinejad ◽  
Mohammad Bayat ◽  
Sadegh Shirian ◽  
Abdolreza Mohamadnia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Young’S Modulus ◽  
Young's Modulus ◽  
Stem Cell Differentiation ◽  
Activity Measurement ◽  
Wisdom Tooth ◽  
Morphological Studies ◽  
Gene And Protein Expression

Abstract Background Bone tissue is one of the tissues that are capable of self-regeneration. However, bone self-regeneration is defeated in the case of broad lesion of bone structure. Isolated stem cells from wisdom tooth follicles can potentially differentiate into ectodermal and mesodermal cells. Saghez is a natural substance that has been extracted from Pistacia terebinthus with unique features, such as high temperature and mechanical stability, adhesive structure, biocompatibility, and anti-neoplastic properties. Methods In this study, Saghez-encapsulated BMP2 was applied as a scaffold for wisdom tooth follicle stem cell differentiation into the osteocyte. A total of three wisdom tooth follicles were obtained for stem cell isolation. For verification of differentiation of the isolated stem cells into osteocyte and adipocyte, Oil Red and Alizarin staining were applied, respectively. Moreover, mesenchymal stem cells were distinguished by profiling their cell surface markers, includingCD73, CD90, CD44, and CD105, by flow cytometry. Saghez scaffold loaded with BMP2 factor was prepared using sol-gel method. Four experimental groups were considered in this study: cells seeded on BMP2 encapsulated in Saghez scaffold, Saghez scaffold, osteogenic medium, and DMEM medium. Results Mechanical properties of Saghez scaffold, including tensile Young’s modulus, ultimate tensile stress, compression Young’s modulus, and complex shear modulus, were 19 MPa, 32 MPa, 0.42 MPa, and 0.9 MPa, respectively. The porosity of the scaffold was 70–140 μm, and the percentage of porosity was 75–98%. The results of flow cytometry studies indicated that CD44, CD73, CD90, and CD105 were positively expressed on the membrane of the tooth follicles’ stem cell. The results indicated that the rate of differentiation of the follicle stem cells into osteocyte was the highest in the Saghez-BMP2 scaffold containing differentiation medium groups. These findings were verified by morphological studies, osteoblast and osteocalcin gene and protein expression investigations, and alkaline phosphatase activity measurement. The highest osteopontin and osteocalcin genes expression levels (1.7 and 1.9) were seen in positive control, followed by DMEM + differentiation factor (1.5 and 1.6), scaffold + BMP2 (1.2 and 1.4), DMEM + stem cell (1 and 1) and scaffold (0.4 and 0.5), and negative control respectively. Conclusion This study provides a novel system for differentiation of the stem cell into osteocytes. The results of this study suggest that loaded BMP2 in Saghez scaffold possibly acts as an osteocyte differentiator factor.

scholarly journals Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

2015 ◽  
Vol 35 (10) ◽  
pp. 1700-1711 ◽  
Author(s):  
Fenfang Chen ◽  
Xia Lin ◽  
Pinglong Xu ◽  
Zhengmao Zhang ◽  
Yanzhen Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Mesenchymal Stem Cell ◽  
Nuclear Export ◽  
Stem Cell Differentiation ◽  
Bmp Signaling ◽  
Dependent Manner ◽  
Mesenchymal Stem Cell Differentiation

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

Magnetic field assisted stem cell differentiation – role of substrate magnetization in osteogenesis

2015 ◽  
Vol 3 (16) ◽  
pp. 3150-3168 ◽  
Author(s):  
Sunil Kumar Boda ◽  
Greeshma Thrivikraman ◽  
Bikramjit Basu
Keyword(s):  
Magnetic Field ◽  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Bone Tissue Engineering ◽  
Human Mesenchymal Stem Cells ◽  
Stem Cell Differentiation

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

scholarly journals Comparison of the Proliferation and Differentiation Potential of Human Urine-, Placenta Decidua Basalis-, and Bone Marrow-Derived Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chengguang Wu ◽  
Long Chen ◽  
Yi-zhou Huang ◽  
Yongcan Huang ◽  
Ornella Parolini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Stem Cell Marker ◽  
Differentiation Potential ◽  
Multipotent Stem Cells ◽  
Decidua Basalis

Human multipotent stem cell-based therapies have shown remarkable potential in regenerative medicine and tissue engineering applications due to their abilities of self-renewal and differentiation into multiple adult cell types under appropriate conditions. Presently, human multipotent stem cells can be isolated from different sources, but variation among their basic biology can result in suboptimal selection of seed cells in preclinical and clinical research. Thus, the goal of this study was to compare the biological characteristics of multipotent stem cells isolated from human bone marrow, placental decidua basalis, and urine, respectively. First, we found that urine-derived stem cells (USCs) displayed different morphologies compared with other stem cell types. USCs and placenta decidua basalis-derived mesenchymal stem cells (PDB-MSCs) had superior proliferation ability in contrast to bone marrow-derived mesenchymal stem cells (BMSCs); these cells grew to have the highest colony-forming unit (CFU) counts. In phenotypic analysis using flow cytometry, similarity among all stem cell marker expression was found, excluding CD29 and CD105. Regarding stem cell differentiation capability, USCs were observed to have better adipogenic and endothelial abilities as well as vascularization potential compared to BMSCs and PDB-MSCs. As for osteogenic and chondrogenic induction, BMSCs were superior to all three stem cell types. Future therapeutic indications and clinical applications of BMSCs, PDB-MSCs, and USCs should be based on their characteristics, such as growth kinetics and differentiation capabilities.

scholarly journals Comparative characterization and osteogenic / adipogenic differentiation of mesenchymal stem cells derived from male rat hair follicles and bone marrow

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Abdel Kader A. Zaki ◽  
Tariq I. Almundarij ◽  
Faten A. M. Abo-Aziza
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Adipogenic Differentiation ◽  
Adult Stem Cell ◽  
Cell Counting ◽  
Population Doubling ◽  
Male Rat ◽  
Cell Source

AbstractClinical applications of cell therapy and tissue regeneration under different conditions need a multiplicity of adult stem cell sources. Up to date, little is available on the comparative isolation, characterization, proliferation, rapid amplification, and osteogenic/adipogenic differentiation of rat mesenchymal stem cells (MSCs) isolated from living bulge cells of the hair follicle (HF) and bone marrow (BM) from the same animal. This work hopes to use HF-MSCs as an additional adult stem cell source for research and application. After reaching 80% confluence, the cell counting, viability %, and yields of HF-MSCs and BM-MSCs were nearly similar. The viability % was 91.41 ± 2.98 and 93.11 ± 3.06 while the cells yield of initial seeding was 33.15 ± 2.76 and 34.22 ± 3.99 and of second passage was 28.76 ± 1.01 and 29.56 ± 3.11 for HF-MSCs and BM-MSCs respectively. Clusters of differentiation (CDs) analysis revealed that HF-MSCs were positively expressed CD34, CD73 and CD200 and negatively expressed CD45. BM-MSCs were positively expressed CD73 and CD200 and negatively expressed of CD34 and CD45. The proliferation of HF-MSCs and BM-MSCs was determined by means of incorporation of Brd-U, population doubling time (PDT) assays and the quantity of formazan release. The percentage of Brd-U positive cells and PDT were relatively similar in both types of cells. The proliferation, as expressed by the quantity of formazan assay in confluent cells, revealed that the quantity of release by BM-MSCs was slightly higher than HF-MSCs. Adipogenic differentiated BM-MSCs showed moderate accumulation of oil red-O stained lipid droplets when compared to that of HF-MSCs which exhibited high stain. The total lipid concentration was significantly higher in adipogenic differentiated HF-MSCs than BM-MSCs (P < 0.05). It was found that activity of bone alkaline phosphatase and calcium concentration were significantly higher (P < 0.01 and P < 0.05 respectively) in osteogenic differentiated BM-MSCs than that of HF-MSCs. The present findings demonstrate that the HF-MSCs are very similar in most tested characteristics to BM-MSCs with the exception of differentiation. Additionally; no issues have been reported during the collection of HF-MSCs. Therefore, the HF may represent a suitable and accessible source for adult stem cells and can be considered an ideal cell source for adipogenesis research.

scholarly journals Dependence of Spreading and Differentiation of Mesenchymal Stem Cells on Micropatterned Surface Area

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Song ◽  
Naoki Kawazoe ◽  
Guoping Chen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Single Cell ◽  
Adipogenic Differentiation ◽  
Cell Spreading ◽  
Poly Vinyl Alcohol ◽  
Cell Array ◽  
Cell Functions

Micropatterning technology is a highly advantageous approach for directly assessing and comparing the effects of different factors on stem cell functions. In this study, poly(vinyl alcohol)- (PVA-) micropatterned polystyrene surfaces were prepared using photoreactive PVA and ultraviolet photolithography with a photomask. The micropatterned surface was suitable for single-cell array formation and long-term cell culture due to the nanometer thickness of nonadhesive PVA layer. Different degrees of cell spreading with the same cell shape were established by adjusting the sizes of circular, cell-adhesive polystyrene micropatterns. Cell spreading and differentiation of mesenchymal stem cells (MSCs) on the micropatterns were investigated at the single-cell level. The assembly and organization of the cytoskeleton were regulated by the degree of cell spreading. Individual MSCs on large circular micropatterns exhibited a more highly ordered arrangement of actin filaments than did those on the small circular micropatterns. Furthermore, the differentiation of MSCs was dependent on the degree of cell spreading. Increased cell spreading facilitated the osteogenic differentiation but suppressed the adipogenic differentiation of MSCs. This micropatterning method is valuable for stem cell research in tissue engineering and regenerative medicine.

Lin28 Enhances Glucose Metabolism in Human Placental Mesenchymal Stem Cells during Hypoxia via the PI3K-Akt Pathway

2021 ◽  
Author(s):  
Xi Zhou ◽  
Junbo Li ◽  
Jin Wang ◽  
Huifang Yang ◽  
Jingzeng Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Glucose Metabolism ◽  
Ischemia Reperfusion ◽  
Stem Cell Differentiation ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Western Blots ◽  
Hypoxic Conditions

Abstract Mesenchymal stem cells (MSCs) are widely used to treat and prevent liver ischemia–reperfusion injury (LIRI), which commonly occurs after liver surgery. Lin28 is an RNA-binding protein crucial for early embryonic development, stem cell differentiation/reprogramming, tumorigenesis, and metabolism. However, whether Lin28 can enhance metabolism in human placental MSCs (PMSCs) during hypoxia to improve the protective effect against LIRI remains unclear. First, a Lin28 overexpression construct was introduced into PMSCs; glucose metabolism, the expression of glucose metabolism - and PI3K-AKT pathway-related proteins, and the levels of microRNA Let-7 family members were examined using a glucose metabolism kit, western blots, and real-time quantitative PCR, respectively. Next, treatment with an AKT inhibitor was performed to understand the association of Lin28 with the PI3K-Akt pathway. Subsequently, AML12 cells were co-cultured with PMSCs to construct an in vitro model of PMSC protecting liver cells from hypoxia injury. Finally, C57BL/6J mice were used to establish a partial warm hepatic ischemia–reperfusion model in vivo. Lin28 increased the glycolysis capacity of PMSCs, allowing these cells to produce more energy under hypoxic conditions. Lin28 also activated PI3K-Akt signaling under hypoxic conditions, and AKT inhibition attenuated the effects of Lin28. In addition, Lin28 overexpression was found to protect cells against LIRI-induced liver damage, inflammation, and apoptosis and attenuate hypoxia-induced hepatocyte injury. Inconclusion, Lin28 enhances glucose metabolism under hypoxic conditions in PMSCs, thereby providing protective effects against LIRI via the activation of the PI3K-Akt signaling pathway. Our study first reported the application of gene-modified mesenchymal stem cell-based therapy in LIRI.

scholarly journals AFM-based Analysis of Wharton’s Jelly Mesenchymal Stem Cells

2019 ◽  
Vol 20 (18) ◽  
pp. 4351
Author(s):  
Renata Szydlak ◽  
Marcin Majka ◽  
Małgorzata Lekka ◽  
Marta Kot ◽  
Piotr Laidler
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Young’S Modulus ◽  
Young's Modulus ◽  
Wharton’S Jelly ◽  
In Vitro Cultivation ◽  
Multipotent Stem Cells ◽  
Wharton's Jelly ◽  
Migration Potential

Wharton’s jelly mesenchymal stem cells (WJ-MSCs) are multipotent stem cells that can be used in regenerative medicine. However, to reach the high therapeutic efficacy of WJ-MSCs, it is necessary to obtain a large amount of MSCs, which requires their extensive in vitro culturing. Numerous studies have shown that in vitro expansion of MSCs can lead to changes in cell behavior; cells lose their ability to proliferate, differentiate and migrate. One of the important measures of cells’ migration potential is their elasticity, determined by atomic force microscopy (AFM) and quantified by Young’s modulus. This work describes the elasticity of WJ-MSCs during in vitro cultivation. To identify the properties that enable transmigration, the deformability of WJ-MSCs that were able to migrate across the endothelial monolayer or Matrigel was analyzed by AFM. We showed that WJ-MSCs displayed differences in deformability during in vitro cultivation. This phenomenon seems to be strongly correlated with the organization of F-actin and reflects the changes characteristic for stem cell maturation. Furthermore, the results confirm the relationship between the deformability of WJ-MSCs and their migration potential and suggest the use of Young’s modulus as one of the measures of competency of MSCs with respect to their possible use in therapy.

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