scholarly journals Romidepsin Promotes Osteogenic and Adipocytic Differentiation of Human Mesenchymal Stem Cells through Inhibition of Histondeacetylase Activity

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Dalia Ali ◽  
Elna P. Chalisserry ◽  
Muthurangan Manikandan ◽  
Rimi Hamam ◽  
Musaad Alfayez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Biological Effects ◽  
Quantitative Polymerase Chain Reaction ◽  
Osteoblastic Differentiation ◽  
Peroxisome Proliferator ◽  
Dual Inhibitor ◽  
Multipotent Stem Cells ◽  
Peroxisome Proliferator Activated Receptor

Bone marrow mesenchymal stem cells (BMSCs) are adult multipotent stem cells that can differentiate into mesodermal lineage cells, including adipocytes and osteoblasts. However, the epigenetic mechanisms governing the lineage-specific commitment of BMSCs into adipocytes or osteoblasts are under investigation. Herein, we investigated the epigenetic effect of romidepsin, a small molecule dual inhibitor targeting HDAC1 and HDAC2 identified through an epigenetic library functional screen. BMSCs exposed to romidepsin (5 nM) exhibited enhanced adipocytic and osteoblastic differentiation. Global gene expression and signaling pathway analyses of differentially expressed genes revealed a strong enrichment of genes involved in adipogenesis and osteogenesis in romidepsin-treated BMSCs during induction into adipocytes or osteoblasts, respectively. Pharmacological inhibition of FAK signaling during adipogenesis or inhibition of FAK or TGFβ signaling during osteogenesis diminished the biological effects of romidepsin on BMSCs. The results of chromatin immunoprecipitation combined with quantitative polymerase chain reaction indicated a significant increase in H3K9Ac epigenetic markers in the promoter regions of peroxisome proliferator-activated receptor gamma (PPARγ) and KLF15 (related to adipogenesis) or SP7 (Osterix) and alkaline phosphatase (ALP) (related to osteogenesis) in romidepsin-treated BMSCs. Our data indicated that romidepsin is a novel in vitro modulator of adipocytic and osteoblastic differentiation of BMSCs.

scholarly journals Diabetic human adipose tissue-derived mesenchymal stem cells fail to differentiate in functional adipocytes

2016 ◽  
Vol 242 (10) ◽  
pp. 1079-1085 ◽  
Author(s):  
Ignazio Barbagallo ◽  
Giovanni Li Volti ◽  
Fabio Galvano ◽  
Guido Tettamanti ◽  
Francesca R Pluchinotta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
In Vitro Study ◽  
Human Adipose Tissue ◽  
Sirtuin 1 ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Adipose tissue dysfunction represents a hallmark of diabetic patients and is a consequence of the altered homeostasis of this tissue. Mesenchymal stem cells (MSCs) and their differentiation into adipocytes contribute significantly in maintaining the mass and function of adult adipose tissue. The aim of this study was to evaluate the differentiation of MSCs from patients suffering type 2 diabetes (dASC) and how such process results in hyperplasia or rather a stop of adipocyte turnover resulting in hypertrophy of mature adipocytes. Our results showed that gene profile of all adipogenic markers is not expressed in diabetic cells after differentiation indicating that diabetic cells fail to differentiate into adipocytes. Interestingly, delta like 1, peroxisome proliferator-activated receptor alpha, and interleukin 1β were upregulated whereas Sirtuin 1 and insulin receptor substrate 1 gene expression were found downregulated in dASC compared to cells obtained from healthy subjects. Taken together our data indicate that dASC lose their ability to differentiate into mature and functional adipocytes. In conclusion, our in vitro study is the first to suggest that diabetic patients might develop obesity through a hypertrophy of existing mature adipocytes due to failure turnover of adipose tissue. Impact statement In the present manuscript, we evaluated the differentiative potential of mesenchymal stem cells (MSCs) in adipocytes obtained from healthy and diabetic patients. This finding could be of great potential interest for the field of obesity in order to exploit such results to further understand the pathophysiological processes underlying metabolic syndrome. In particular, inflammation in diabetic patients causes a dysfunction in MSCs differentiation and a decrease in adipocytes turnover leading to insulin resistance.

Mesenchymal Stem Cells in Infantile Hemangioma Reside in the Perivascular Region

2012 ◽  
Vol 15 (1) ◽  
pp. 5-12 ◽  
Author(s):  
Si-Ming Yuan ◽  
Rong-Liang Chen ◽  
Wei-Min Shen ◽  
Hai-Ni Chen ◽  
Xiao-Jun Zhou
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle Actin ◽  
Infantile Hemangioma ◽  
Peroxisome Proliferator ◽  
Alpha Smooth Muscle Actin ◽  
Peroxisome Proliferator Activated Receptor ◽  
Multiple Organs ◽  
Ppar Γ

Infantile hemangioma grows quickly in the first year of life and regresses slowly to fibrofatty tissue during childhood; mesenchymal stem cells (MSCs) have been reported to contribute to this adipogenesis. Recent studies have shown the perivascular origin of MSCs in multiple organs. We hypothesized that MSCs in hemangioma might also reside in the perivascular region. We isolated MSCs from proliferating hemangioma by their selective adhesion to plastic culture dishes. Mesenchymal stem cells from bone marrow (BM-MSCs) and foreskin-derived fibroblasts were used as controls. Flow cytometry and immunofluorescence staining were used to examine their antigen profiles; in vitro induction of multi-lineage differentiation was performed to test their pluripotency. Platelet-derived growth factor R-β (PDGFR-β), CD133, and peroxisome-proliferator-activated receptor gamma (PPAR-γ) were selected as the markers to observe MSCs in hemangioma by immunohistochemistry staining, with costaining of CD31 and alpha-smooth muscle actin (α-SMA). Hemangioma-derived MSCs (Hem-MSCs) had fibroblast-like morphology; they expressed the MSC markers CD105, CD90, CD29, and vimentin and did not express the hematopoietic/endothelial markers CD45, CD34, CD31, and flt-1; Hem-MSCs also expressed CD133 and PPAR-γ. Most Hem-MSCs expressed PDGFR-β and α-SMA; in contrast, the expression of PDGFR-β and α-SMA in BM-MSCs was very weak. The Hem-MSCs differentiated into adipocytes, osteoblasts, and chondroblasts in vitro. This confirmed their pluripotency. Immunohistochemistry showed the colocalization of PDGFR-β/α-SMA, CD133/α-SMA, and PPAR-γ/α-SMA in the perivascular region. MSCs were successfully obtained from proliferating hemangioma, revealing the perivascular origin of MSCs in hemangioma.

scholarly journals Myeloma cells shift osteoblastogenesis to adipogenesis by inhibiting the ubiquitin ligase MURF1 in mesenchymal stem cells

2020 ◽  
Vol 13 (633) ◽  
pp. eaay8203 ◽  
Author(s):  
Zhiqiang Liu ◽  
Huan Liu ◽  
Jin He ◽  
Pei Lin ◽  
Qiang Tong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Direct Consequence ◽  
Peroxisome Proliferator ◽  
Integrin Subunit ◽  
Peroxisome Proliferator Activated Receptor ◽  
Myeloma Cells

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro coculture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 integrin subunit on myeloma cells stimulated vascular cell adhesion molecule–1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger protein-1 (MURF1)–mediated ubiquitylation of peroxisome proliferator–activated receptor γ2 (PPARγ2). Stabilized PPARγ2 proteins enhanced adipogenesis and consequently reduced osteoblastogenesis from MSCs, thus suppressing bone formation in vitro and in vivo. These findings reveal that suppressed bone formation is a direct consequence of myeloma-MSC contact that promotes the differentiation of MSCs into adipocytes at the expense of osteoblasts. Thus, this study provides a potential strategy for treating bone resorption in patients with myeloma by counteracting tumor-MSC interactions.

scholarly journals The Novel Role of PGC1α in Bone Metabolism

2021 ◽  
Vol 22 (9) ◽  
pp. 4670
Author(s):  
Cinzia Buccoliero ◽  
Manuela Dicarlo ◽  
Patrizia Pignataro ◽  
Francesco Gaccione ◽  
Silvia Colucci ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Osteoblastic Differentiation ◽  
In Vivo Studies ◽  
Peroxisome Proliferator ◽  
Sirtuin 3 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) is a protein that promotes transcription of numerous genes, particularly those responsible for the regulation of mitochondrial biogenesis. Evidence for a key role of PGC1α in bone metabolism is very recent. In vivo studies showed that PGC1α deletion negatively affects cortical thickness, trabecular organization and resistance to flexion, resulting in increased risk of fracture. Furthermore, in a mouse model of bone disease, PGC1α activation stimulates osteoblastic gene expression and inhibits atrogene transcription. PGC1α overexpression positively affects the activity of Sirtuin 3, a mitochondrial nicotinammide adenina dinucleotide (NAD)-dependent deacetylase, on osteoblastic differentiation. In vitro, PGC1α overexpression prevents the reduction of mitochondrial density, membrane potential and alkaline phosphatase activity caused by Sirtuin 3 knockdown in osteoblasts. Moreover, PGC1α influences the commitment of skeletal stem cells towards an osteogenic lineage, while negatively affects marrow adipose tissue accumulation. In this review, we will focus on recent findings about PGC1α action on bone metabolism, in vivo and in vitro, and in pathologies that cause bone loss, such as osteoporosis and type 2 diabetes.

scholarly journals Biological effects of bone marrow mesenchymal stem cells on hepatitis B virus in vitro

2017 ◽  
Vol 15 (5) ◽  
pp. 2551-2559 ◽  
Author(s):  
Wei-Ping Zheng ◽  
Bo-Ya Zhang ◽  
Zhong-Yang Shen ◽  
Ming-Li Yin ◽  
Yi Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Biological Effects ◽  
B Virus ◽  
Marrow Mesenchymal Stem Cells

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.

scholarly journals Enhanced Therapeutic Potential of the Secretome Released from Adipose-Derived Stem Cells by PGC-1α-Driven Upregulation of Mitochondrial Proliferation

2019 ◽  
Vol 20 (22) ◽  
pp. 5589
Author(s):  
Jaeim Lee ◽  
Ok-Hee Kim ◽  
Sang Chul Lee ◽  
Kee-Hwan Kim ◽  
Jin Sun Shin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Injury ◽  
Therapeutic Potential ◽  
Tissue Expression ◽  
In Vitro Models ◽  
Peroxisome Proliferator ◽  
Adipose Derived Stem Cells ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome proliferator activated receptor λ coactivator 1α (PGC-1α) is a potent regulator of mitochondrial biogenesis and energy metabolism. In this study, we investigated the therapeutic potential of the secretome released from the adipose-derived stem cells (ASCs) transfected with PGC-1α (PGC-secretome). We first generated PGC-1α-overexpressing ASCs by transfecting ASCs with the plasmids harboring the gene encoding PGC-1α. Secretory materials released from PGC-1α-overexpressing ASCs were collected and their therapeutic potential was determined using in vitro (thioacetamide (TAA)-treated AML12 cells) and in vivo (70% partial hepatectomized mice) models of liver injury. In the TAA-treated AML12 cells, the PGC-secretome significantly increased cell viability, promoted expression of proliferation-related markers, such as PCNA and p-STAT, and significantly reduced the levels of reactive oxygen species (ROS). In the mice, PGC-secretome injections significantly increased liver tissue expression of proliferation-related markers more than normal secretome injections did (p < 0.05). We demonstrated that the PGC-secretome does not only have higher antioxidant and anti-inflammatory properties, but also has the potential of significantly enhancing liver regeneration in both in vivo and in vitro models of liver injury. Thus, reinforcing the mitochondrial antioxidant potential by transfecting ASCs with PGC-1α could be one of the effective strategies to enhance the therapeutic potential of ASCs.

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