The Molecular Mechanism Underlying the Proliferating and Preconditioning Effect of Vitamin C on Adipose-Derived Stem Cells

Kim, Ji Hye; Kim, Wang Kyun; Sung, Young Kwan; Kwack, Mi Hee; Song, Seung Yong; Choi, Joon Seok; Park, Sang Gyu; Yi, TacGhee; Lee, Hyun Joo; Kim, Dae Duk; Seo, Hyun Ook; Song, Sun U.; Sung, Jong Hwan

doi:10.1089/scd.2013.0460

Cited by 44 publications

(46 citation statements)

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“…Hypoxia also accelerated the adipogenic differentiation of ASCs via mitochondrial ROS generation [29]. In addition, vitamin C significantly increased ASC proliferation through the mitogen-activated protein kinase pathway and enhanced the hair-growth promoting effect of ASCs [10]. Furthermore, platelet-derived growth factor (PDGF)-B and -D increased the proliferation of ASCs via ROS generation, and preconditioning by PDGF-D significantly enhanced the hair-growth promoting effect of ASCs [28,36].…”

Section: Discussionmentioning

confidence: 99%

“…The next day, the cells were treated with MA (1, 5, 10, and 50 mM) for 48 hours. The medium was then removed, and cell numbers were counted using the Cell Counting Kit-8 (CCK-8) assay (Dojindo Molecular Technologies Inc., Rockville, MD, http://www.dojindo.com) [10]. The cells were treated with 10% CCK-8 solution in the medium for 4 hours, and the absorbance was measured at 450 nm using a microplate reader (Tecan, Grödig, Austria, http://www.tecan.com).…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

“…Next, the cells were seeded on 48-well plates or 60-mm dishes, and the siRNA mixtures were transfected into the cells for 24 hours [10]. Silencing was evaluated using quantitative real-time polymerase chain reaction (qPCR).…”

Section: Small Interfering Rna Transfectionmentioning

confidence: 99%

“…Although an unexpanded SVF has been clinically applied, ASCs are usually expanded to acquire large numbers of cells for therapeutic applications. Pharmacological stimuli such as sphingosylphosphocholine, lysophosphatidic acid, and vitamin C have been used to increase the production yield and regenerative potential of ASCs [8][9][10]. However, transplanted ASCs encounter harmful environments, which mitigate their building-block function and survival.…”

Section: Introductionmentioning

confidence: 99%

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Megestrol Acetate Increases the Proliferation, Migration, and Adipogenic Differentiation of Adipose-Derived Stem Cells via Glucocorticoid Receptor

Sung

Jeong

et al. 2015

Stem Cells Translational Medicine

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Because adipose-derived stem cells (ASCs) are usually expanded to acquire large numbers of cells for therapeutic applications, it is important to increase the production yield and regenerative potential during expansion. Therefore, a tremendous need exists for alternative ASC stimuli during cultivation to increase the proliferation and adipogenic differentiation of ASCs. The present study primarily investigated the involvement of megestrol acetate (MA), a progesterone analog, in the stimulation of ASCs, and identifies the target receptors underlying stimulation. Mitogenic and adipogenic effects of MA were investigated in vitro, and pharmacological inhibition and small interfering (si) RNA techniques were used to identify the molecular mechanisms involved in the MA-induced stimulation of ASCs. MA significantly increased the proliferation, migration, and adipogenic differentiation of ASCs in a dose-dependent manner. Glucocorticoid receptor (GR) is highly expressed compared with other nuclear receptors in ASCs, and this receptor is phosphorylated after MA treatment. MA also upregulated genes downstream of GR in ASCs, including ANGPTL4, DUSP1, ERRF11, FKBP5, GLUL, and TSC22D3. RU486, a pharmacological inhibitor of GR, and transfection of siGR significantly attenuated MA-induced proliferation, migration, and adipogenic differentiation of ASCs. Although the adipogenic differentiation potential of MA was inferior to that of dexamethasone, MA had mitogenic effects in ASCs. Collectively, these results indicate that MA increases the proliferation, migration, and adipogenic differentiation of ASCs via GR phosphorylation. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:789-799 SIGNIFICANCEMagestrol acetate (MA) increases the proliferation, migration, and adipogenic differentiation of adipose-derived stem cells (ASCs) via glucocorticoid receptor phosphorylation. Therefore, MA can be applied to increase the production yield during expansion and can be used to facilitate adipogenic differentiation of ASCs.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Proliferation Assaymentioning

confidence: 99%

Section: Small Interfering Rna Transfectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Megestrol Acetate Increases the Proliferation, Migration, and Adipogenic Differentiation of Adipose-Derived Stem Cells via Glucocorticoid Receptor

Sung

Jeong

et al. 2015

Stem Cells Translational Medicine

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“…In this regard, various preconditioning strategies are being currently explored to improve the survival of stem and progenitor cells to be used for transplantation in injured tissues. These strategies include preconditioning the stem cells by treatment with chemokines, growth factors, or pharmacological agents (Sheng et al, 2013;Kim et al, 2014;Sun et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Diazoxide preconditioning of endothelial progenitor cells improves their ability to repair the infarcted myocardium

Mehmood

Muhammad

Khan

et al. 2015

Cell Biology International

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Reduced survival and homing of the transplanted cells in the oxidative stressed ischemic environment limits the potential outcome of cell therapies for myocardial ischemia. Diazoxide (DZ), a highly selective mitochondrial ATP sensitive K(+) channel opener, is known to improve the survival and therapeutic ability of mesenchymal stem cells and skeletal myoblasts for the repair of heart failure. The current study explored the effect of DZ preconditioning in improving the ability of endothelial progenitor cells (EPCs) to counteract, in vitro oxidative stress, and to repair the infarcted myocardium. The EPCs were preconditioned by 30 min incubation with 200 μM DZ followed by exposure to 200 μM hydrogen peroxide (H2 O2 ) for 2 h. Non-preconditioned EPCs with and without exposure to H2 O2 were used as control. DZ preconditioning of EPCs resulted in significantly reduced cell injury as shown by reduced lactate dehydrogenase release and expression of annexin V-PE in comparison to untreated EPCs. Furthermore, DZ preconditioned EPCs exhibited upregulated expression of prosurvival genes (VEGF, SDF-1α, PCNA, and Bcl2 ), improved chemokines release (VEGF, IGF, and SDF-1α), viability, Akt phosphorylation and tube formation. In vivo experiments involved transplantation of DZ preconditioned and untreated EPCs in the left ventricle after permanent ligation of left anterior descending coronary artery in rats. The results demonstrated that DZ EPCs transplanted group showed significant reduction in infarct size along with robust cell proliferation, angiogenesis and improvement in cardiac function. The current study demonstrates that DZ preconditioning enhances EPCs survival under oxidative stress in vitro and their ability to treat myocardial infarction.

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Functional Regulation of Adipose-Derived Stem Cells by PDGF-D

et al. 2015

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Platelet-derived growth factor-D (PDGF-D) was recently identified, and acts as potent mitogen for mesenchymal cells. PDGF-D also induces cellular transformation and promotes tumor growth. However, the functional role of PDGF-D in adipose-derived stem cells (ASCs) has not been identified. Therefore, we primarily investigated the autocrine and paracrine roles of PDGF-D in this study. Furthermore, we identified the signaling pathways and the molecular mechanisms involved in PDGF-D-induced stimulation of ASCs. It is of interest that PDGF-B is not expressed, but PDGF-D and PDGF receptor-b are expressed in ASCs. PDGF-D showed the strongest mitogenic effect on ASCs, and PDGF-D regulates the proliferation and migration of ASCs through the PI3K/Akt pathways. PDGF-D also increases the proliferation and migration of ASCs through generation of mitochondrial reactive oxygen species (mtROS) and mitochondrial fission. mtROS generation and fission were mediated by p66Shc phosphorylation, and BCL2-related protein A1 and Serpine peptidase inhibitor, clade E, member 1 mediated the proliferation and migration of ASCs. In addition, PDGF-D upregulated the mRNA expression of diverse growth factors such as vascular endothelial growth factor A, fibroblast growth factor 1 (FGF1), FGF5, leukemia inhibitory factor, inhibin, beta A, interleukin 11, and heparin-binding EGF-like growth factor. Therefore, the preconditioning of PDGF-D enhanced the hair-regenerative potential of ASCs. PDGF-D-induced growth factor expression was attenuated by a pharmacological inhibitor of mitogen-activated protein kinase pathway. In summary, PDGF-D is highly expressed by ASCs, where it acts as a potent mitogenic factor. PDGF-D also upregulates growth factor expression in ASCs. Therefore, PDGF-D can be considered a novel ASC stimulator, and used as a preconditioning agent before ASC transplantation. STEM CELLS 2015;33:542-556

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The Molecular Mechanism Underlying the Proliferating and Preconditioning Effect of Vitamin C on Adipose-Derived Stem Cells

Cited by 44 publications

References 47 publications

Megestrol Acetate Increases the Proliferation, Migration, and Adipogenic Differentiation of Adipose-Derived Stem Cells via Glucocorticoid Receptor

Megestrol Acetate Increases the Proliferation, Migration, and Adipogenic Differentiation of Adipose-Derived Stem Cells via Glucocorticoid Receptor

Diazoxide preconditioning of endothelial progenitor cells improves their ability to repair the infarcted myocardium

Functional Regulation of Adipose-Derived Stem Cells by PDGF-D

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