Adipocytes Differentiated In Vitro from Rat Mesenchymal Stem Cells Lack Essential Free Fatty Acids Compared to Adult Adipocytes

Bojin, Florina; Gruia, Alexandra T.; Cristea, Mirabela; Ordodi, Valentin; Păunescu, Virgil; Mic, Felix A.

doi:10.1089/scd.2011.0491

Cited by 12 publications

(9 citation statements)

References 14 publications

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“…Nonetheless, BMSCs failed to generate adipocytes when injected into the adipose tissue (Koh et al, ), suggesting that differentiation from BMSCs into adipocytes may not take place in vivo, and, therefore, the lipid accumulation inside BMSCs might occur by other mechanisms than lipogenesis and has other functional significance. Our previously published results (Bojin et al, ) showed that BMSCs‐derived adipocytes and adipocytes from the adipose tissue do not share the same composition in FFAs, suggesting that BMSCs‐derived adipocytes and adipocytes from the adipose tissue are not structurally and functionally equivalent, even though the culture medium contains serum with lipoproteins that could be easily uptaken by the BMSCs‐derived adipocytes. In this paper, we examined the differentiation of BMSCs into an adipocyte phenotype and the role of autophagy in the intra‐cellular accumulation of lipid in the BMSCs‐derived adipocytes.…”

Section: Discussionmentioning

confidence: 92%

Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets

Gruia

Suciu

Barbu–Tudoran

et al. 2015

Journal Cellular Physiology

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Adult bone marrow mesenchymal stromal cells (BMSCs) can easily be differentiated into a variety of cells. In vivo transplantation of BMSCs-differentiated cells has had limited success, suggesting that these cells may not be fully compatible with the cells they are intended to replace in vivo. We investigated the structural and functional features of BMSCs-derived adipocytes as compared with adipocytes from adipose tissue, and the structure and functionality of lipid vesicles formed during BMSCs differentiation to adipocytes. Gas chromatography-mass spectrometry showed fatty acid composition of BMSCs-derived adipocytes and adipocytes from the adipose tissue to be very different, as is the lipid rafts composition, caveolin-1 expression, caveolae distribution in their membranes, and the pattern of expression of fatty acid elongases. Confocal microscopy confirmed the absence from BMSCs-derived adipocytes of markers of lipid droplets. BMSCs-derived adipocytes cannot convert deuterated glucose into deuterated species of fatty acids and cannot uptake the deuterated fatty acid-bovine serum albumin complexes from the culture medium, suggesting that intra-cellular accumulation of lipids does not occur by lipogenesis. We noted that BMSCs differentiation to adipocytes is accompanied by an increase in autophagy. Autophagic vesicles accumulate in the cytoplasm of BMSCs-derived adipocytes and their size and distribution resembles that of Nile Red-stained lipid vesicles. Stimulation of autophagy in BMSCs triggers the intra-cellular accumulation of lipids, while inhibition of autophagy prevents this accumulation. In conclusion, differentiation of BMSCs-derived adipocytes leads to intra-cellular accumulation of autophagic vesicles rather than functional lipid droplets, suggesting that these cells are not authentic adipocytes. J. Cell. Physiol. 231: 863-875, 2016. © 2015 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 92%

Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets

Gruia

Suciu

Barbu–Tudoran

et al. 2015

Journal Cellular Physiology

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“…However, significant differences have been observed in their responsiveness to adipocyte differentiation signals, as subcutaneous adipose tissue-derived stem cells (ASC) are better to differentiate to adipocytes compared to BMSC. BM and extramedullary adipocytes are different in cell size, expression of stem cell markers (e.g., Sox2, Nanog, Klf4), presence of extracellular matrix, free fatty acid content, proportion of immune cells in contact with adipocytes, levels of cytokine, and adipokine expression ( 23 – 28 ). Also BMSC have higher expression of inflammatory genes compared to ASC ( 29 ).…”

Section: Bone Marrow Adipocytes Versus Extramedullary Adipocytesmentioning

confidence: 99%

The Bone Marrow-Derived Stromal Cells: Commitment and Regulation of Adipogenesis

2016

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Bone marrow (BM) microenvironment represents an important compartment of bone that regulates bone homeostasis and the balance between bone formation and bone resorption depending on the physiological needs of the organism. Abnormalities of BM microenvironmental dynamics can lead to metabolic bone diseases. BM stromal cells (also known as skeletal or mesenchymal stem cells) [bone marrow stromal stem cell (BMSC)] are multipotent stem cells located within BM stroma and give rise to osteoblasts and adipocytes. However, cellular and molecular mechanisms of BMSC lineage commitment to adipocytic lineage and regulation of BM adipocyte formation are not fully understood. In this review, we will discuss recent findings pertaining to identification and characterization of adipocyte progenitor cells in BM and the regulation of differentiation into mature adipocytes. We have also emphasized the clinical relevance of these findings.

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“…and indicated increased methionine and FAs levels (and non-detectable creatine) as characteristic of adipogenesis. Subsequent reports employed MS metabolomics, with hBMMSC lipid extracts unveiling changes in free FAs throughout adipogenesis [23,24]. MSC-differentiated preadipocytes (days 5-7) and adipocytes (day 21) lacked specific elongases (possibly hindering endogenous polyunsaturated FA, PUFA, synthesis) and differed from primary adipocytes in decreased levels of LA, -linolenic acid (ALA) and arachidonic acid (AA); and increased docosahexaenoic acid (DHA).…”

Section: Adipogenesismentioning

confidence: 99%

Metabolomic Applications in Stem Cell Research: a Review

Bispo

Jesus

Marques

et al. 2021

Stem Cell Rev and Rep

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This review describes the use of metabolomics to study stem cell (SC) characteristics and function (excluding SCs in cancer research, suited to a fully dedicated text). The interest in employing metabolomics in SC research has consistently grown and emphasis is, here, given to developments reported in the past five years. This text informs on the existing methodologies and their complementarity regarding the information provided, comprising untargeted/targeted approaches, which couple mass spectrometry or nuclear magnetic resonance spectroscopy with multivariate analysis (and, in some cases, pathway analysis and integration with other omics), and more specific analytical approaches, namely isotope tracing to highlight particular metabolic pathways, or in tandem microscopic strategies to pinpoint characteristics within a single cell. The bulk of this review covers the existing applications in various aspects of mesenchymal SC behavior, followed by pluripotent and neural SCs, with a few reports addressing other SC types. Some of the central ideas investigated comprise the metabolic/biological impacts of different tissue/donor sources and differentiation conditions, including the importance of considering 3D culture environments, mechanical cues and/or media enrichment to guide differentiation into specific lineages. Metabolomic analysis has considered cell endometabolomes and exometabolomes (fingerprinting and footprinting, respectively), having measured both lipid species and polar metabolites involved in a variety of metabolic pathways. This review clearly demonstrates the current enticing promise of metabolomics in significantly contributing towards a deeper knowledge on SC behavior, and the discovery of new biomarkers of SC behavior and function with potential translation to in vivo clinical practice.

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Adipocytes Differentiated In Vitro from Rat Mesenchymal Stem Cells Lack Essential Free Fatty Acids Compared to Adult Adipocytes

Cited by 12 publications

References 14 publications

Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets

Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets

The Bone Marrow-Derived Stromal Cells: Commitment and Regulation of Adipogenesis

Metabolomic Applications in Stem Cell Research: a Review

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