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01.01.2013 | Article

A diabetic milieu promotes OCT4 and NANOG production in human visceral-derived adipose stem cells

verfasst von: P. Dentelli, C. Barale, G. Togliatto, A. Trombetta, C. Olgasi, M. Gili, C. Riganti, M. Toppino, M. F. Brizzi

Erschienen in: Diabetologia | Ausgabe 1/2013

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Abstract

Aims/hypothesis

Successful outcomes have been obtained by exploiting adipose-derived stem cells (ASCs) in regenerative medicine. NADPH oxidase (NOX)-generated reactive oxygen species (ROS) are known to control stem cell self-renewal. Several high glucose (HG)-mediated effects depend on NOX-generated ROS. In this study, we investigated whether, and how mechanistically, HG concentrations control ASC fate in patients with diabetes.

Methods

ASCs from the visceral adipose tissue of non-diabetic (N-ASCs) and diabetic participants (D-ASCs), identified by surface markers, were counted and evaluated for ROS generation and stem cell properties. Their ability to release soluble factors was assessed by BioPlex analysis. To reproduce an in vitro diabetic glucose milieu, N-ASCs were cultured in HG (25 mmol/l) or normal glucose (NG) concentration (5 mmol/l), as control. ASC pluripotency was assessed by in vitro study. The p47^phox NOX subunit, AKT and octamer-binding transcription factor 4 (OCT4; also known as POU5F1) were knocked down by small-interfering RNA technology. Stem-cell features were evaluated by sphere cluster formation.

Results

The ASC number was higher in diabetic patients than in non-diabetic controls. Production of OCT4 and NANOG, stem-cell-specific transcription factors, was upregulated in D-ASCs compared with N-ASCs. Moreover, we found that ROS production and AKT activation drove D-ASC, but not N-ASC, secretion. When N-ASCs were cultured in vitro in the presence of HG, they also expressed OCT4/NANOG and formed spheres. By knock-down of the p47^phox NOX subunit, AKT and OCT4 we demonstrated that NOX-generated ROS and their downstream signals are crucial for HG-mediated ASC de-differentiation and proinflammatory cytokine production.

Conclusions/interpretation

We herein provide a rationale for exploiting D-ASCs in regenerative medicine and/or exploiting HG preconditioning to increase ASCs ex vivo.

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Schaffler A, Buchler C (2007) Concise review: adipose tissue-derived stromal cells—basic and clinical implications for novel cell-based therapies. Stem Cells 25:818–827PubMedCrossRef

Le Blanc K, Ringdén O (2007) Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 262:509–525PubMedCrossRef

Tran TT, Kahn CR (2010) Transplantation of adipose tissue and stem cells: role in metabolism and disease. Nat Rev Endocrinol 6:195–213PubMedCrossRef

Rubina K, Kalinina N, Efimenko A et al (2009) Adipose stromal cells stimulate angiogenesis via promoting progenitor cell differentiation, secretion of angiogenic factors, and enhancing vessel maturation. Tissue Eng Part A 15:2039–2050PubMedCrossRef

Zuk PA, Zhu M, Ashjian P et al (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295PubMedCrossRef

Baglioni S, Francalanci M, Squecco R et al (2009) Characterization of human adult stem-cell populations isolated from visceral and subcutaneous adipose tissue. FASEB J 23:3494–3505PubMedCrossRef

Gimble JM, Katz JA, Bunnell BA (2007) Adipose derived stem cells for regenerative medicine. Circ Res 100:1249–1260PubMedCrossRef

Locke M, Feisst V, Dunbar PR (2011) Concise review: human adipose-derived stem cells: separating promise from clinical need. Stem Cells 29:404–411PubMedCrossRef

Yarak S, Okamoto OK (2010) Human adipose-derived stem cells: current challenges and clinical perspectives. An Bras Dermatol 85:647–656PubMedCrossRef

10.

Roldan M, Macias-Gonzalez M, Garcia R, Tinahones FJ, Martin M (2011) Obesity short-circuits stemness gene network in human adipose multipotent stem cells. FASEB J 25:4111–4126PubMedCrossRef

11.

Schraufstatter IU, Discipio RG, Khaldoyanidi S (2011) Mesenchymal stem cells and their microenvironment. Front Biosci 17:2271–2288CrossRef

12.

Horwitz EM, Dominici M (2008) How do mesenchymal stromal cells exert their therapeutic benefit? Cytotherapy 10:771–774PubMedCrossRef

13.

Ng HH, Surani MA (2011) The transcriptional and signalling networks of pluripotency. Nat Cell Biol 13:490–496PubMedCrossRef

14.

Kuroda T, Tada M, Kubota H et al (2005) Octamer and Sox elements are required for transcriptional cis regulation of NANOG gene expression. Mol Cell Biol 25:2475–2485PubMedCrossRef

15.

Loh YH, Wu Q, Chew JL et al (2006) The OCT4 and NANOG transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38:431–440PubMedCrossRef

16.

Silva J, Chambers I, Pollard S, Smith A (2006) NANOG promotes transfer of pluripotency after cell fusion. Nature 441:997–1001PubMedCrossRef

17.

Lengner CJ, Welstead GG, Jaenisch R (2008) The pluripotency regulator OCT4: a role in somatic stem cells? Cell Cycle 7:725–728PubMedCrossRef

18.

Park IH, Zhao R, West JA et al (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141–146PubMedCrossRef

19.

Santourlidis S, Wernet P, Ghanjati F et al (2011) Unrestricted somatic stem cells (USSC) from human umbilical cord blood display uncommitted epigenetic signatures of the major stem cell pluripotency genes. Stem Cell Res 6:60–69PubMedCrossRef

20.

Freberg CT, Dahl JA, Timoskainen S, Collas P (2007) Epigenetic reprogramming of OCT4 and NANOG regulatory regions by embryonal carcinoma cell extract. Mol Biol Cell 18:1543–1553PubMedCrossRef

21.

Goodell MA (2003) Stem-cell “plasticity”: befuddled by the muddle. Curr Opin Hematol 10:208–213PubMedCrossRef

22.

Sanges D, Cosma MP (2010) Reprogramming cell fate to pluripotency: the decision-making signalling pathways. Int J Dev Biol 54:1575–1587PubMedCrossRef

23.

Kim JH, Jee MK, Lee SY et al (2009) Regulation of adipose tissue stromal cells behaviors by endogenic OCT4 expression control. PLoS One 4:e7166PubMedCrossRef

24.

Lambeth JD, Krause KH, Clark RA (2008) NOX enzymes as novel targets for drug development. Semin Immunopathol 30:339–363PubMedCrossRef

25.

Jang YY, Sharkis SJ (2007) A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 110:3056–3063PubMedCrossRef

26.

Le Belle JE, Orozco NM, Paucar AA et al (2011) Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/AKT-dependant manner. Cell Stem Cell 8:59–71PubMedCrossRef

27.

Kim JH, Park SH, Park SG, Choi JS, Xia Y, Sung JH (2011) The pivotal role of reactive oxygen species generation in the hypoxia-induced stimulation of adipose-derived stem cells. Stem Cells Dev 20:1753–1761PubMedCrossRef

28.

Kakehi T, Yabe-Nishimura (2008) NOX enzymes and diabetic complications. Semin Immunopathol C 30:301–314CrossRef

29.

Zhang P, Moudgill N, Hager E et al (2011) Endothelial differentiation of adipose-derived stem cells from elderly patients with cardiovascular disease. Stem Cells Dev 20:977–988PubMedCrossRef

30.

Dentelli P, Rosso A, Olgasi C, Camussi G, Brizzi MF (2011) IL-3 is a novel target to interfere with tumor vasculature. Oncogene 30:4930–4940PubMedCrossRef

31.

Togliatto G, Trombetta A, Dentelli P, Rosso A, Brizzi MF (2011) MIR221/MIR222-driven post-transcriptional regulation of P27KIP1 and P57KIP2 is crucial for high-glucose- and AGE-mediated vascular cell damage. Diabetologia 54:1930–1940PubMedCrossRef

32.

Togliatto G, Trombetta A, Dentelli P et al (2010) Unacylated ghrelin rescues endothelial progenitor cell function in individuals with type 2 diabetes. Diabetes 59:1016–1025PubMedCrossRef

33.

Dentelli P, Trombetta A, Togliatto G et al (2009) Formation of STAT5/PPARgamma transcriptional complex modulates angiogenic cell bioavailability in diabetes. Arterioscler Thromb Vasc Biol 29:114–120PubMedCrossRef

34.

Liu TM, Martina M, Hutmacher DW, Hui JH, Lee EH, Lim B (2007) Identification of common pathways mediating differentiation of bone marrow- and adipose tissue-derived human mesenchymal stem cells into three mesenchymal lineages. Stem Cells 25:750–760PubMedCrossRef

35.

Heumüller S, Sven W, Barbosa-Sicard E et al (2008) Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension 51:211–217PubMedCrossRef

36.

Babior BM (2004) NADPH oxidase. Curr Opin Immunol 16:42–47PubMedCrossRef

37.

Brand MD, Affourtit C, Esteves TC et al (2004) Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med 37:755–767PubMedCrossRef

38.

Reynolds BA, Weiss S (1996) Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol 175:1–13PubMedCrossRef

39.

Carrière A, Ebrahimian TG, Dehez S et al (2009) Preconditioning by mitochondrial reactive oxygen species improves the proangiogenic potential of adipose-derived cells-based therapy. Arterioscler Thromb Vasc Biol 29:1093–1099PubMedCrossRef

40.

Calle MC, Fernandez ML (2012) Inflammation and type 2 diabetes. Diabetes Metab 38:183–191PubMedCrossRef

41.

Maumus M, Peyrafitte JA, D’Angelo R et al (2011) Native human adipose stromal cells: localization, morphology and phenotype. Int J Obes (Lond) 35:1141–1153CrossRef

42.

Li L, Xie T (2005) Stem cell niche: structure and function. Annu Rev Cell Dev Biol 21:605–631PubMedCrossRef

43.

Simon HU, Haj-Yehia A, Levi-Schaffer F (2000) Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 5:415–418PubMedCrossRef

44.

Park SG, Kim JH, Xia Y, Sung JH (2011) Generation of reactive oxygen species in adipose-derived stem cells: friend or foe? Expert Opin Ther Targets 15:1297–1306PubMedCrossRef

45.

Noble M, Pröschel C, Mayer-Pröschel M (2011) Oxidative-reductionist approaches to stem and progenitor cell function. Cell Stem Cell 8:1–2PubMedCrossRef

46.

Garrido AM, Griendling KK (2009) NADPH oxidases and angiotensin II receptor signaling. Mol Cell Endocrinol 302:148–158PubMedCrossRef

47.

Waki H, Tontonoz P (2007) Endocrine functions of adipose tissue. Annu Rev Pathol 2:31–56PubMedCrossRef

48.

Pradhan AD, Manson JE, Rifai N et al (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334PubMedCrossRef

49.

Fisher G, Hyatt TC, Hunter GR et al (2012) Markers of inflammation and fat distribution following weight loss in African-American and white women. Obesity (Silver Spring) 20:715–720CrossRef

50.

Thörne A, Lönnqvist F, Apelman J, Hellers G, Arner P (2002) A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord 26:193–199PubMedCrossRef

Titel: A diabetic milieu promotes OCT4 and NANOG production in human visceral-derived adipose stem cells
verfasst von: P. Dentelli
C. Barale
G. Togliatto
A. Trombetta
C. Olgasi
M. Gili
C. Riganti
M. Toppino
M. F. Brizzi
Publikationsdatum: 01.01.2013
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 1/2013
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-012-2734-7

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A diabetic milieu promotes OCT4 and NANOG production in human visceral-derived adipose stem cells

Abstract

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