Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets.
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.
Regional Center for Immunology of Transplantation, Clinical Emergency County Hospital, 10 Iosif Bulbuca Blvd. 300736, Timisoara, Romania.
Alexandra T
AT
Gruia
Department of Functional Sciences, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq. 300041, Timisoara, Romania.
Maria
M
Suciu
Electron Microscopy Center, Babes-Bolyai University Cluj, Cluj Napoca, Romania.
Lucian
L
Barbu-Tudoran
Department of Functional Sciences, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq. 300041, Timisoara, Romania.
Seyed Mohammad Reza
SM
Azghadi
Regional Center for Immunology of Transplantation, Clinical Emergency County Hospital, 10 Iosif Bulbuca Blvd. 300736, Timisoara, Romania.
Mirabela I
MI
Cristea
Department of Functional Sciences, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq. 300041, Timisoara, Romania.|Faculty of Animal Sciences and Biotechnologies, Banat's University of Agricultural Sciences and Veterinary Medicine, Timisoara, Romania.
Dragos V
DV
Nica
Department of Microscopical Morphology-Morphopathology, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timisoara, Romania.
Adrian
A
Vaduva
Department of Pathophysiology, "Victor Babeş" University of Medicine and Pharmacy of Timişoara, 14 Tudor Vladimirescu st. 300173, Timisoara, Romania.
Danina
D
Muntean
Department of Functional Sciences, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq. 300041, Timisoara, Romania.|INCD "Victor Babes" Bucuresti, Romania.
Ani Aurora
AA
Mic
Department of Functional Sciences, "Victor Babes" University of Medicine and Pharmacy, 2 Eftimie Murgu Sq. 300041, Timisoara, Romania.
Felix A
FA
Mic
D000123:Acetyltransferases / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001343:Autophagy; D001854:Bone Marrow Cells / Q000166:cytology; D021941:Caveolae / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D003903:Deuterium / Q000378:metabolism; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism*; D050155:Lipogenesis; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids; D003903:Deuterium; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D005947:Glucose