Abstract—
Protocols of adipogenic differentiation for mesenchymal stem cells (MSC) are mostly based on addition of various inducers, including rosiglitazone, a. specific agonist of PPARG facilitated the differentiation in this lineage. Rosiglitazone was not used for induction of adipogenic differentiation of fetal MSC from bone marrow (fMSC-BM). Here we described adipogenic differentiation induced by rosiglitazone in fMSC-BM (FetMSC). We found that the number of differentiated cells was 31.0 ± 1.9% (Oil Red O staining n = 1121). Expression of PPARG gene, a key adipogenic regulator, increased during differentiation. It is demonstrated that fMSC-BM generated adipocytes in the differentiation medium with rosiglitazone.
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REFERENCES
Abdallah, B.M., Al-Shammary, A., Skagen, P., Abu, Dawud, R., Adjaye, J., Aldahmash, A., and Kassem, M., CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal cells, Stem Cell Res., 2015, vol. 15, pp. 449–458.
Baghbaderani, B.A., Behie, L.A., Sen, A., Mukhida, K., Hong, M., and Mendez, I., Expansion of human neural precursor cells in large-scale bioreactors for the treatment of neurodegenerative disorders, Biotechnol. Prog., 2008, vol. 24, pp. 859–870.
Balbi, C. and Bollini, S., Fetal and perinatal stem cells in cardiac regeneration: moving forward to the paracrine era, Placenta, 2017, vol. 59, pp. 96–106.
Bazargan, M., Foster, D., Jr., Muhlhausler, B.S., Morrison, J.L., McMillen, C., and Davey, A.K., Limited fetal metabolism of rosiglitazone: elimination via the maternal compartment in the pregnant ewe, Reprod. Toxicol., 2016, vol. 61, pp. 162–168.
Bredella, A.M., Torriani, M., Ghomi, R.G., Thomas, B.J., Danielle, J.Brick, D.J., Gerweck, A.V., Rosen, C.J., Klibanski, A.A., and Karen, K.M., Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women, Obesity (Silver Spring), 2011, vol. 19, pp. 49–53.
Darlington, G.J., Ross, S.E., and MacDougald, O.A., The role of C/EBP genes in adipocyte differentiation, J. Biol. Chem., 1998, vol. 273, pp. 30057–30060.
Farmer, S.R., Transcriptional control of adipocyte formation, Cell Metab., 2006, vol. 4, pp. 263–273.
Friedenstein, A.J., Osteogenic stem cells in bone marrow, in Bone and Mineral Research, Amsterdam: Elsevier, 1990, pp. 243–272.
Gorzelniak, K., Janke, J., Engeli, S., and Sharma, A.M., Validation of endogenous controls for gene expression studies in human adipocytes and preadipocytes, Horm. Metab. Res., 2001, vol. 33, pp. 625–627.
Guan, H.P., Ishizuka, T., Chui, P.C., Lehrke, M., and Lazar, M.A., Corepressors selectively control the transcriptional activity of PPARgamma in adipocytes, Genes Dev., 2005, vol. 19, pp. 453–461.
Kalyoncu, N.I., Yaris, F., Ulku, C., Kadioglu, M., Kesim, M., Unsal, M., Dikici, M., and Yaris, E., A case of rosiglitazone exposure in the second trimester of pregnancy, Reprod. Toxicol., 2005, vol. 19, pp. 563–564.
Kawai, M., and Rosen, C.J., PPARg: a circadian transcription factor in adipogenesis and osteogenesis, Nat. Rev. Endocrinol., 2010, vol. 6, pp. 629–636.
Kawai, M., Sousa, K.M., MacDougald, O.A., and Rosen, C.J., The many facets of PPARgamma: novel insights for the skeleton, Am. J. Physiol. Endocrinol. Metab., 2010, vol. 299, pp. 299–318.
Krylova, T.A., Koltsova, A.M., Zenin, V.V., Musorina, A.S., Yakovleva, T.K., and Poljanskaya, G.G., Comparative characteristics of new mesenchymal stem cell lines derived from human embryonic stem cells, bone marrow and foreskin, Tsitologiia, 2012, vol. 54, no. 1, pp. 5–16.
Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., and Komeda, K., PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance, Mol. Cell., 1999, vol. 4, pp. 597–609.
Landon, M.B. and Gabbe, S.G., Diabetes in pregnancy, in High Risk Pregnancy: Management Options, London: WB Saunders, 1999, pp. 665–684.
Liu, G.P., Liao, C.H., and Xu, Y.P., Proliferation and adipogenic differentiation of human adipose-derived stem cells isolated from middle-aged patients with prominent orbital fat in the lower eyelids, Plast. Aesthet. Res., 2016, vol. 3, pp. 322–327.
Livak, K.J. and Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method, Methods, 2001, vol. 25, pp. 402–408.
Meuelman, N., Tondreau, T., Delforqe, A., Dejeneffe, M., Massy, M., Libertalis, M., Bron, D., and Laqneaux, L., Human marrow mesenchymal stem cell culture: serum-free medium allows better expansion than classical alpha-MEM medium, Eur. J. Haematol., 2006, vol. 76, pp. 309–316.
Ntambi, J.M. and Young-Cheul, K., Adipocyte differentiation and gene expression, J. Nutr., 2000, vol. 130, pp. 3122S–3126S.
O’Donoghue, K. and Fisk, N.M., Fetal stem cells, Best Pract. Res.Clin. Obstet. Gynaecol., 2004, vol. 18, pp. 853–875.
Olefsky, J.M., Treatment of insulin resistance with peroxisome proliferator–activated receptor γ agonists, J. Clin. Invest., 2000, vol. 106, pp. 467–472.
Pittenger, M.F., Mackay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., Moorman, M.A., Simonetti, D.W., Craig, S., and Marshak, D.R., Multilineage potential of adult human mesenchymal stem cells, Science, 1999, vol. 284, pp. 143–147.
Polymeri, A., Giannobile, W.V., and Kaigler, D., Bone marrow stromal stem cells in tissue engineering and regenerative medicine, Horm. Metab. Res., 2016, vol. 48, pp. 700–713.
Post, S., Abdallah, B.M., Bentzon, J.F., and Kassem, M., Demonstration of the presence of independent pre-osteoblastic and pre-adipocytic cell populations in bone marrow-derived mesenchymal stem cells, Bone, 2008, vol. 43, pp. 32–39.
Revittser, A., Pivovarova, O., Rudovich, N., Pfeiffer, A.F.H., Shlyakto, E., and Dmitrieva, R., PPARg and natriuretic peptides (NP) pathway are alterated in adipose tissue from heart failure patients/ mesenchymal stromal cells (MMSC) as a tool to study cardiovascular metabolic disorders in vitro, Cardivasc. Res., 2014, vol. 103, p. s105.
Rosen, E.D. and MacDougald, O.A., Adipocyte differentiation from the inside out, Nat. Rev. Mol. Cell Biol., 2006, vol. 7, pp. 885–896.
Rosen, E.D. and Spiegelman, B.M., Molecular regulation of adipogenesis, Ann. Rev. Cell Devel. Biol., 2000, vol. 16, pp. 145–171.
Russo, G.T., Giandalia, A., Romeo, E.L., Nunziata, M., Muscianisi, M., Ruffo, M.C., Catalano, A., and Cucinotta, D., Fracture risk in type 2 diabetes, Curr. Persp., Gender Differ. Int. J. Endocrinol., 2016, pp. 1615–1735.
Tontonoz, P., Hu, E., Graves, R.A., Budavari, A.I., and Spiegelman, B.M., mPPARgamma 2: tissue-specific regulator of an adipocyte enhancer, Genes Dev., 1994a, vol. 10, pp. 1224–1234.
Tontonoz, P., Hu, E., and Spiegelman, B.M., Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor, Cell, 1994b, vol. 79, pp. 1147–1156.
Turner, P.A., Gurumurthy, B., Bailey, J.L., Elks, C.E., and Janorkar, A.V., Adipogenic differentiation of human adipose-derived stem cells grown as spheroids, Process. Biochem., 2017, vol. 59, pp. 312–320.
Wang, L., Waltenberger, B., Pferschy-Wenzig, E.M., Blunder, M., Liu, X., Malainer, C., Blazevic, T., Schwaiger, S., Rollinger, J.M., Heiss, E.H., Schuster, D., Kopp, B., Bauer, R., Stuppner, H., Dirsch, V.M., and Atanasov, A.G., Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review, Biochem. Pharmacol., 2014, vol. 92, pp. 73–89.
Watanabe, M., Inukai, K., Katagiri, H., Awata, T., Oka, Y., and Katayama, S., Regulation of PPAR gamma transcriptional activity in 3T3-L1 adipocytes, Biochem. Biophys. Res. Commun., 2003, vol. 300, pp. 429–436.
Willson, T.M., Lambert, M.H., and Kliewer, S.A., Peroxisome proliferator–activated receptor γ and metabolic disease, Annu. Rev. Biochem., 2001, vol. 70, pp. 341–367.
Witt, R., MacKenzie, T.C., and Peranteau, W.H., Fetal stem cell and gene therapy, Semin. Fetal Neonatal Med., 2017, vol. 22, pp. 410–414.
Wongdee, K. and Charoenphandhu, N., Osteoporosis in diabetes mellitus: possible cellular and molecular mechanisms, World J. Diabetes, 2011, vol. 2, pp. 41–48.
Yaris, F., Yaris, E., Kadioglu, M., Ulku, C., Kesim, M., and Kalyoncu, N.I., Normal pregnancy outcome following inadvertent exposure to rosiglitazone, gliclazide, and atorvastatin in a diabetic and hypertensive woman, Reprod. Toxicol., 2004, vol. 18, pp. 619–621.
Zebisch, K., Voigt, V., Wabitsch, M., and Brandsch, M., Protocol for effective differentiation of 3T3-L1 cells to adipocytes, Anal. Biochem., 2012, vol. 425, pp. 88–90.
ACKNOWLEDGMENTS
We are grateful to S.B. Semenova and I.O. Vasilieva (Institute of Cytology, Russian Academy of Sciences) for help in preparing the manuscript for publication.
This work was supported by the Russian Foundation for Basic Research, project no. 16-34-00952.
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Translated by I. Fridlyanskaya
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Revittser, A.V., Neguliaev, Y.A. Adipogenic Differentiation of Human Mesenchymal Stem Cells Derived from Fetal Bone Marrow Using Rosiglitazone. Cell Tiss. Biol. 12, 367–372 (2018). https://doi.org/10.1134/S1990519X18050061
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DOI: https://doi.org/10.1134/S1990519X18050061