scholarly journals Evaluation of Oxidative Stress and Mitophagy during Adipogenic Differentiation of Adipose-Derived Stem Cells Isolated from Equine Metabolic Syndrome (EMS) Horses

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Krzysztof Marycz ◽  
Christine Weiss ◽  
Agnieszka Śmieszek ◽  
Katarzyna Kornicka
Keyword(s):  
Metabolic Syndrome ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Protective Mechanism ◽  
Autophagic Flux ◽  
Isolated Cells ◽  
Differentiation Potential ◽  
Equine Metabolic Syndrome ◽  
Major Factors

Mesenchymal stem cells (MSCs) are frequently used in both human and veterinary medicine because their unique properties, such as modulating the immune response and differentiating into multiple lineages, make them a valuable tool in cell-based therapies. However, many studies have indicated the age-, lifestyle-, and disease-related deterioration of MSC regenerative characteristics. However, it still needs to be elucidated how the patient’s health status affects the effectiveness of MSC differentiation. In the present study, we isolated mesenchymal stem cells from adipose tissue (adipose-derived mesenchymal stem cells (ASCs)) from horses diagnosed with equine metabolic syndrome (EMS), a common metabolic disorder characterized by pathological obesity and insulin resistance. We investigated the metabolic status of isolated cells during adipogenic differentiation using multiple research methods, such as flow cytometry, PCR, immunofluorescence, or transmission and confocal microscopy. The results indicated the impaired differentiation potential of ASCEMS. Excessive ROS accumulation and ER stress are most likely the major factors limiting the multipotency of these cells. However, we observed autophagic flux during differentiation as a protective mechanism that allows cells to maintain homeostasis and remove dysfunctional mitochondria.

scholarly journals Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Chad M. Teven ◽  
Xing Liu ◽  
Ning Hu ◽  
Ni Tang ◽  
Stephanie H. Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Epigenetic Regulation ◽  
Adult Stem Cells ◽  
Es Cells ◽  
Adipogenic Differentiation ◽  
Embryonic Stem ◽  
Cell Types ◽  
Differentiation Potential ◽  
Msc Differentiation

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Owing to their ease of isolation and unique characteristics, MSCs have been widely regarded as potential candidates for tissue engineering and repair. While various signaling molecules important to MSC differentiation have been identified, our complete understanding of this process is lacking. Recent investigations focused on the role of epigenetic regulation in lineage-specific differentiation of MSCs have shown that unique patterns of DNA methylation and histone modifications play an important role in the induction of MSC differentiation toward specific lineages. Nevertheless, MSC epigenetic profiles reflect a more restricted differentiation potential as compared to ES cells. Here we review the effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation. We also highlight clinical applications of MSC epigenetics and nuclear reprogramming.

scholarly journals The Effect of Early Rounds of ex vivo Expansion and Cryopreservation on the Adipogenic Differentiation Capacity of Adipose-Derived Stromal/Stem Cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
C. Durandt ◽  
C. Dessels ◽  
C. da Silva ◽  
C. Murdoch ◽  
M. S. Pepper
Keyword(s):  
Stem Cells ◽  
Ex Vivo ◽  
Adipogenic Differentiation ◽  
Isolated Cells ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Surface Marker Expression ◽  
Cd36 Expression ◽  
The Impact ◽  
Stromal Stem Cells

Abstract Multipotent adipose-derived stromal/stem cells (ASCs) are candidates for use in cellular therapies for the treatment of a variety of conditions/diseases. Ex vivo expansion of freshly isolated ASCs may be necessary prior to clinical application to ensure that clinically relevant cell numbers are administered during treatment. In addition, cryopreserving cells at early passages allows for storage of freshly isolated cells for extended periods of time before expanding these cells for clinical usage. There are however several concerns that these laboratory-based procedures may alter the characteristics of the cells and in so doing decrease their regenerative potential. In this study we report on the impact of early rounds of cryopreservation (P0) and ex vivo expansion (P0 to P5) on the phenotypic characteristics and adipogenic differentiation potential of ASCs. Our results show that ASCs that upregulate CD36 expression during adipogenic differentiation gradually decrease with increasing expansion rounds. The consequent decrease in adipogenic differentiation capacity was evident in both gene expression and flow cytometry-based phenotypic studies. Successive rounds of expansion did not however alter cell surface marker expression of the cells. We also show that early cryopreservation of ASCs (at P0) does not affect the adipogenic differentiation potential of the cells.

scholarly journals The Influence of Aging on the Regenerative Potential of Human Adipose Derived Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Monika Marędziak ◽  
Krzysztof Marycz ◽  
Krzysztof A. Tomaszewski ◽  
Katarzyna Kornicka ◽  
Brandon Michael Henry
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Population Doubling ◽  
Osteogenic Potential ◽  
Population Doubling Time ◽  
Joint Diseases ◽  
Differentiation Potential ◽  
Age Related

Tissue regeneration using human adipose derived mesenchymal stem cells (hASCs) has significant potential as a novel treatment for many degenerative bone and joint diseases. Previous studies have established that age negatively affects the proliferation status and the osteogenic and chondrogenic differentiation potential of mesenchymal stem cells. The aim of this study was to assess the age-related maintenance of physiological function and differentiation potential of hASCs in vitro. hASCs were isolated from patients of four different age groups: (1) >20 years (n=7), (2) >50 years (n=7), (3) >60 years (n=7), and (4) >70 years (n=7). The hASCs were characterized according to the number of fibroblasts colony forming unit (CFU-F), proliferation rate, population doubling time (PDT), and quantified parameters of adipogenic, chondrogenic, and osteogenic differentiation. Compared to younger cells, aged hASCs had decreased proliferation rates, decreased chondrogenic and osteogenic potential, and increased senescent features. A shift in favor of adipogenic differentiation with increased age was also observed. As many bone and joint diseases increase in prevalence with age, it is important to consider the negative influence of age on hASCs viability, proliferation status, and multilineage differentiation potential when considering the potential therapeutic applications of hASCs.

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 Mapping SOX9 transcriptional dynamics during multi-lineage differentiation of human mesenchymal stem cells

2021 ◽  
Author(s):  
Kannan Govindaraj ◽  
Sakshi Khurana ◽  
Marcel Karperien ◽  
Janine Nicole Post
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Single Cell ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Differentiation Potential ◽  
Lineage Differentiation ◽  
Transcriptional Dynamics

The master transcription factor SOX9 is a key player during chondrocyte differentiation, cartilage development, homeostasis and disease. Modulation of SOX9 and its target gene expression is essential during chondrogenic, osteogenic and adipogenic differentiation of human mesenchymal stem cells (hMSCs). However, lack of sufficient knowledge about the signaling interplay during differentiation remains one of the main reasons preventing successful application of hMSCs in regenerative medicine. We previously showed that Transcription Factor - Fluorescence Recovery After Photobleaching (TF-FRAP) can be used to study SOX9 dynamics at the single cell level. We showed that changes in SOX9 dynamics are linked to its transcriptional activity. Here, we investigated SOX9 dynamics during differentiation of hMSCs into the chondrogenic, osteogenic and adipogenic lineages. We show that there are clusters of cells in hMSCs with distinct SOX9 dynamics, indicating that there are a number of subpopulations present in the heterogeneous hMSCs. SOX9 dynamics data at the single cell resolution revealed novel insights about its activity in these subpopulations (cell types). In addition, the response of SOX9 to differentiation stimuli varied in these subpopulations. Moreover, we identified donor specific differences in the number of cells per cluster in undifferentiated hMSCs, and this correlated to their differentiation potential.

scholarly journals Soft substrate maintains proliferative and adipogenic differentiation potential of human mesenchymal stem cells on long-term expansion by delaying senescence

Biology Open ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. bio039453 ◽  
Author(s):  
Sanjay Kumar Kureel ◽  
Pankaj Mogha ◽  
Akshada Khadpekar ◽  
Vardhman Kumar ◽  
Rohit Joshi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Soft Substrate ◽  
Differentiation Potential

scholarly journals Effect of 20(S)-Hydroxycholesterol on Multilineage Differentiation of Mesenchymal Stem Cells Isolated from Compact Bones in Chicken

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1360
Author(s):  
Roshan Adhikari ◽  
Chongxiao Chen ◽  
Woo Kyun Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Health ◽  
Hedgehog Signaling ◽  
Myogenic Differentiation ◽  
Adipogenic Differentiation ◽  
Bioactive Molecules ◽  
Marker Genes ◽  
Human Mscs ◽  
Differentiation Potential

Bone health and body weight gain have significant economic and welfare importance in the poultry industry. Mesenchymal stem cells (MSCs) are common progenitors of different cell lineages such as osteoblasts, adipocytes, and myocytes. Specific oxysterols have shown to be pro-osteogenic and anti-adipogenic in mouse and human MSCs. To determine the effect of 20(S)-hydroxycholesterol (20S) on osteogenic, adipogenic, and myogenic differentiation in chicken, mesenchymal stem cells isolated from compact bones of broiler chickens (cBMSCs) were subjected to various doses of 20S, and markers of lineage-specific mRNA were analyzed using real-time PCR and cell cytochemistry. Further studies were conducted to evaluate the molecular mechanisms involved in lineage-specific differentiation pathways. Like human and mouse MSCs, 20S oxysterol expressed pro-osteogenic, pro-myogenic, and anti-adipogenic differentiation potential in cBMSCs. Moreover, 20(S)-Hydroxycholesterol induced markers of osteogenic genes and myogenic regulatory factors when exposed to cBMSCs treated with their specific medium. In contrast, 20S oxysterol suppressed expression of adipogenic marker genes when exposed to cBMSCs treated with OA, an adipogenic precursor of cBMSCs. To elucidate the molecular mechanism by which 20S exerts its differentiation potential in all three lineages, we focused on the hedgehog signaling pathway. The hedgehog inhibitor, cyclopamine, completely reversed the effect of 20S induced expression of osteogenic and anti-adipogenic mRNA. However, there was no change in the mRNA expression of myogenic genes. The results showed that 20S oxysterol promotes osteogenic and myogenic differentiation and decreases adipocyte differentiation of cBMSCs. This study also showed that the induction of osteogenesis and adipogenesis inhibition in cBMSCs by 20S is mediated through the hedgehog signaling mechanism. The results indicated that 20(S) could play an important role in the differentiation of chicken-derived MSCs and provided the theory basis on developing an intervention strategy to regulate skeletal, myogenic, and adipogenic differentiation in chicken, which will contribute to improving chicken bone health and meat quality. The current results provide the rationale for the further study of regulatory mechanisms of bioactive molecules on the differentiation of MSCs in chicken, which can help to address skeletal health problems in poultry.

scholarly journals Bone Marrow Mesenchymal Stem Cells from Acute Myelogenous Leukemia Patients Demonstrate Adipogenic Differentiation Propensity

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5064-5064
Author(s):  
Mitra Azadniv ◽  
Jason R. Myers ◽  
Helene McMurray ◽  
John M. Ashton ◽  
Naxin Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Pathway Analysis ◽  
Adipogenic Differentiation ◽  
Myelogenous Leukemia ◽  
Normal Donor ◽  
Differentiation Potential ◽  
Airway Pathology ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Bone marrow mesenchymal stem cells (BMSCs) constitute one of the important cellular components of the hematopoietic microenvironmental niche. These cells are capable of differentiation into osteoprogenitors which comprise part of the endosteal niche. In vivo studies have shown that depletion of BMSCs resulted in reduction of hematopoietic stem cell content, and there is direct in vitro evidence that BMSCs are able to support both normal and leukemia progenitor cell proliferation and survival and contribute to leukemia cell resistance to cytotoxic therapies. Whether BMSCs from leukemia marrow differ from normal counterparts and how they contribute to and are influenced by the leukemia environmental niche are still incompletely understood. In this work we sought to compare normal and AML-derived BMSCs and to define the propensity of BMSCs from leukemia patients for osteogenic or adipogenic differentiation. Methods: BMSCs were isolated from marrow aspirates of normal donor and AML patients using standard methodologies. Donors were age-matched to the leukemia patients to the extent possible in each comparative experiment. Such cells met the definition of MSCs in that they were adherent and expressed CD73, CD90, CD44, CD117 and CD105 and had osteoblastic and adipogenic differentiation capabilities. All comparisons were done at comparable passage number between samples. Results: BMSCs from AML donors demonstrated irregular vs. spindle shaped morphology as compared with BMSCs from younger donors <50 years of age but similar morphology to those grown from older donors. AML derived BMSCs were larger and had slower growth rate as assessed by longer passage times during lower passages (41 vs. 21 days). Cell surface expression markers were similar between normal and AML. CFU-F outgrowth was less from AML as compared to normal BMSC, and no difference in osteogenic differentiation was noted by Alizarin Red S measurement. On the other hand, lipid droplet formation measured by Oil Red O during adipogenic differentiation induction was greater in the AML BMSCs as compared with age matched controls, suggesting increased adipogenic differentiation potential. To determine if we could detect a gene signature difference between AML and normal BMSCs which would predict adipogenic propensity, RNA-Seq analysis was performed on AML and normal donor specimens(n=3 in each group), all from subjects >50 years of age using CuffDiff (v2.0.2). This identified 88 genes differentially expressed between the two groups. A heat map was generated using Euclidean distance hierarchical clustering of gene expression values from individual samples. This readily grouped AML vs. normal samples. Pathway analysis using Ingenuity Pathway Analysis (IPA) predicted dysregulation of four canonical pathways in AML-BMSCs as compared to normal BMSCs. These included 1) Role of tissue factor in cancer, 2) Airway pathology in COPD, 3) Oleate biosynthesis, and 4) Adipogenesis. The last two pathways are consistent with the biological observation of enhanced adipogenesis in AML-derived BMSCs. IPA analysis proposed a model of altered adipogenic differentiation in AML-BMSCs attributable to lower expression of two key regulatory genes, SOX9 and EGR2. Reduced expression of SOX9 and EGR2 in AML BMSCs as compared to normal BMSCs was validated by qRT-PCR and western blot analysis. SOX9 is reported to contribute to the commitment of MSCs to adipogenic phenotype through negative influence on expression of key transcription factors in adipogenesis, and ERG2 downregulation is required in some systems for adipocyte lineage commitment. Conclusion: Understanding the role that adipogenic MSCs play during leukemia evolution and treatment could offer insight into pathogenesis and potential therapies for these disorders. Disclosures Liesveld: Onconova: Other: Data safety monitoring board; Astex: Honoraria; glycomimetics: Research Funding.

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