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Karger Publishers, Cells Tissues Organs, 3(203), p. 153-172, 2016

DOI: 10.1159/000447628

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PPAR Agonists Promote the Differentiation of Porcine Bone Marrow Mesenchymal Stem Cells into the Adipogenic and Myogenic Lineages

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

<b><i>Purpose:</i></b> The aim of this work was to evaluate the effect of PPAR agonists on the differentiation and metabolic features of porcine mesenchymal stem cells induced to the adipogenic or myogenic lineages. <b><i>Methods:</i></b> Bone marrow MSCs from neonate pigs were isolated and identified by cell proliferation, cell surface markers or the gene expression of stem cells (CD44, CD90, CD105 or <i>Oct4 </i>and<i> Nanog</i>, respectively). Cells were differentiated into adipose or muscle cells and treated with the PPAR agonists; adipogenic and myogenic differentiation was promoted by adding these compounds. The expression of <i>PPAR&#x03B3;</i> (an adipose marker) and <i>MyoD1</i> and <i>MyHC</i> (muscle markers), metabolic changes and expression levels of metabolic enzymes involved in glycolysis, lipogenesis, lipolysis and the pentose phosphate pathway were tested by qPCR. <b><i>Results:</i></b> MSCs from neonate pigs exhibited high proliferation and were positive for CD44, CD90 and CD105 markers and <i>Oct4 </i>and<i> Nanog</i> expression. The treatment that promoted the highest expression of <i>PPAR&#x03B3;</i> was 50 µ<smlcap>M</smlcap> of conjugated linoleic acid (CLA) c9 t11 (6.44 ± 0.69-fold, p ≤ 0.0001) in the adipose differentiation, and upregulation of <i>HX2, ACCAα, ATGL, LPL</i> and <i>G6DP</i> (p ≤ 0.0001) and downregulation of <i>PFK</i> and <i>ACCAβ</i> (p ≤ 0.0001) were found. For muscle differentiation, the best treatment was 50 µ<smlcap>M</smlcap> of CLA c10 t12 (59.72 ± 4.72-fold, p ≤ 0.0001), and metabolic changes were upregulation of <i>PFK</i>, <i>ACCAβ</i>, <i>G6DP</i>, <i>CPT1</i> and <i>PPARβ/δ</i> (p ≤ 0.0001), but no effect was observed with <i>HX2</i> and <i>ACCAα</i> (p ≥ 0.05). <b><i>Conclusions:</i></b> Our results suggest that differentiated cells exhibit a typical cell lineage metabolism and higher efficiencies both in anabolism and catabolism.