Pyrvinium, a potent small molecule Wnt inhibitor, increases engraftment and inhibits lineage commitment of mesenchymal stem cells (MSCs)

Wound Repair and Regeneration

Volumn 20, Issue 2, 2012, Pages 185-193

  Saraswati, Sarika ^a   Deskins, Desirae L ^a,b   Holt, Ginger E ^a   Young, Pampee P ^a,b  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ACTIN; BETA CATENIN; PYRVINIUM EMBONATE; WNT PROTEIN; WNT3A PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BONE DEVELOPMENT; CARTILAGE CELL; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; CELL REGENERATION; CELL RENEWAL; CELL SURVIVAL; CELL THERAPY; CONTROLLED STUDY; CYTOPLASM; DRUG EFFECT; DRUG POTENCY; GRANULATION TISSUE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MESENCHYMAL STEM CELL; MOUSE; NONHUMAN; OSTEOCYTE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; WOUND;

ANIMALS; BETA CATENIN; CELL DIFFERENTIATION; CELL PROLIFERATION; CELLS, CULTURED; GRANULATION TISSUE; MESENCHYMAL STEM CELLS; MICE; MICE, INBRED C57BL; MICE, INBRED NOD; MICE, SCID; PYRVINIUM COMPOUNDS; SIGNAL TRANSDUCTION; WNT PROTEINS; WOUND HEALING;

EID: 84858111380     PISSN: 10671927     EISSN: 1524475X     Source Type: Journal    
DOI: 10.1111/j.1524-475X.2012.00767.x     Document Type: Article

References (44)

1. Pittenger MF, Martin BJ,. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 2004; 95: 9-20. (Pubitemid 38931831)
2. Tropel P, Noel D, Platet N, Legrand P, Benabid A, Berger F,. Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res 2004; 295: 395-406. (Pubitemid 38490494)
3. Alfaro MP, Pagni M, Vincent A, Atkinson J, Hill MF, Cates J, Davidson JM, Rottman J, Lee E, Young PP,. A Wnt modulator sFRP2 enhances mesenchymal stem cell engraftment, granulation tissue formation and myocardial repair. Proc Natl Acad Sci U S A 2008; 105: 18366-18371.
4. Mirotsou M, Zhang Z, Deb A, Zhang L, Gnecchi M, Noiseux N, Mu H, Pachori A, Dzau V,. Secreted frizzled related protein 2 (sFRP2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci U S A 2007; 104: 1643-1648. (Pubitemid 46214644)
5. Alfaro MP, Young PP,. Lessons from genetically altered mesenchymal stem cells (MSCs); candidates for improved MSC-directed myocardial repair. Cell Transplant 2011 Nov 11;. Pubmed PMID: 22080676.
6. Cleland JG, Coletta AP, Abdellah AT, Cullington D, Clark AL, Rigby AS,. Clinical trials update from the American Heart Association 2007: CORONA, RethinQ, MASCOT, AF-CHF, HART, MASTER, POISE and stem cell therapy. Eur J Heart Fail 2008; 10: 102-108.
7. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE, Brenner MK,. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 1999; 5: 309-313. (Pubitemid 29124367)
8. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P,. Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410: 701-705. (Pubitemid 32290358)
9. Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL,. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 2003; 423: 409-414. (Pubitemid 36626987)
10. Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH,. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 2004; 10: 55-63. (Pubitemid 38524699)
11. Oerlemans MI, Goumans MJ, van, Middelaar B, Clevers H, Doevendans PA, Sluijter JP,. Active Wnt signaling in response to cardiac injury. Basic Res Cardiol 2010; 105: 631-641.
12. Cadigan KM,. Wnt-beta-catenin signaling. Curr Biol 2008; 18: R943-947.
13. Baurand A, Zelarayan L, Betney R, Gehrke C, Dunger S, Noack C, Busjahn A, Huelsken J, Taketo MM, Birchmeier W, Dietz R, Bergmann MW,. {beta}-catenin downregulation is required for adaptive cardiac remodeling. Circ Res 2007; 100: 1353-1362. (Pubitemid 46742926)
14. Malekar P, Hagenmueller M, Anyanwu A, Buss S, Streit MR, Weiss CS, Wolf D, Riffel J, Bauer A, Katus HA, Hardt SE,. Wnt signaling is critical for maladaptive cardiac hypertrophy and accelerates myocardial remodeling. Hypertension 2010; 55: 939-945.
15. Chen B, Dodge ME, Tang W, Lu J, Ma Z, Fan C, Wei S, Hao W, Kilgore J, Williams NS, Roth MG, Amatruda JF, Chen C, Lum L,. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol 2009; 5: 100-107.
16. Shan J, Shi DL, Wang J, Zheng J,. Identification of a specific inhibitor of the dishevelled PDZ domain. Biochemistry 2005; 44: 15495-15503. (Pubitemid 41706133)
17. Thorne CA, Hanson AJ, Schneider J, Tahinci E, Orton D, Cselenyi CS, Jernigan KK, Meyers KC, Hang BI, Waterson AG, Kim K, Melancon B, Ghidu VP, Sulikowski GA, LaFleur B, Salic A, Lee LA, Miller DM 3rd, Lee E,. Small-molecule inhibition of Wnt signaling through activation of casein kinase 1alpha. Nat Chem Biol 2010; 6: 829-836.
18. Alfaro MP, Vincent A, Saraswati S, Thorne CA, Hong CC, Lee E, Young PP,. sFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial repair. J Biol Chem 2010; 285: 35645-35653.
19. Saraswati S, Alfaro MP, Thorne CA, Atkinson J, Lee E, Young PP,. Pyrvinium, a potent small molecule Wnt inhibitor, promotes wound repair and post-MI cardiac remodeling. PLoS ONE 2010; 5 (11): e15521. doi: 10.1371/journal.pone.0015521. Pubmed PMID: 21170416; PubMed Central PMCID: PMC2993965.
20. Romanov YA, Darevskaya AN, Merzlikina NV, Buravkova LB,. Mesenchymal stem cells from human bone marrow and adipose tissue: isolation, characterization, and differentiation potentialities. Bull Exp Biol Med 2005; 140: 138-143. (Pubitemid 41548650)
21. Hofling AA, Vogler C, Creer MH, Sands MS,. Engraftment of human CD34+ cells leads to widespread distribution of donor-derived cells and correction of tissue pathology in a novel murine xenotransplantation model of lysosomal storage disease. Blood 2003; 101: 2054-2063. (Pubitemid 36237614)
22. Glaser JH, Sly WS,. Beta-glucuronidase deficiency mucopolysaccharidosis: methods for enzymatic diagnosis. J Lab Clin Med 1973; 82: 969-977.
23. Young PP, Vogler C, Hofling AA, Sands MS,. Biodistribution and efficacy of donor T lymphocytes in a murine model of lysosomal storage disease. Mol Ther 2003; 7: 52-61. (Pubitemid 36305358)
24. Cooney R, Iocono J, Maish G, Smith JS, Ehrlich P,. Tumor necrosis factor mediates impaired wound healing in chronic abdominal sepsis. J Trauma 1997; 42: 415-420. (Pubitemid 27155076)
25. Augello A, De Bari C,. The regulation of differentiation in mesenchymal stem cells. Hum Gene Ther 2010; 21: 1226-1238.
26. Barry FP,. Biology and clinical applications of mesenchymal stem cells. Birth Defects Res C Embryo Today 2003; 69: 250-256. (Pubitemid 37238402)
27. Jorgensen C, Gordeladze J, Noel D,. Tissue engineering through autologous mesenchymal stem cells. Curr Opin Biotechnol 2004; 15: 406-410. (Pubitemid 39304035)
28. ClinicalTrials.gov; 2011; Available at (last accessed 30 September 2011).
29. Parekkadan B, Milwid JM,. Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng 2010; 12: 87-117.
30. Satija NK, Gurudutta GU, Sharma S, Afrin F, Gupta P, Verma YK, Singh VK, Tripathi RP,. Mesenchymal stem cells: molecular targets for tissue engineering. Stem Cells Dev 2007; 16: 7-23. (Pubitemid 46362588)
31. He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, Tian Q, Zeng X, He X, Wiedemann LM, Mishina Y, Li L,. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 2004; 36: 1117-1121. (Pubitemid 41184475)
32. Kirstetter P, Anderson K, Porse BT, Jacobsen SE, Nerlov C,. Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block. Nat Immunol 2006; 7: 1048-1056. (Pubitemid 44420649)
33. Qyang Y, Martin-Puig S, Chiravuri M, Chen S, Xu H, Bu L, Jiang X, Lin L, Granger A, Moretti A, Caron L, Wu X, Clarke J, Taketo MM, Laugwitz KL, Moon RT, Gruber P, Evans SM, Ding S, Chien KR,. The renewal and differentiation of Isl1+ cardiovascular progenitors are controlled by a Wnt/beta-catenin pathway. Cell Stem Cell 2007; 1: 165-179. (Pubitemid 47224618)
34. Kondo T, Matsuoka AJ, Shimomura A, Koehler KR, Chan RJ, Miller JM, Srour EF, Hashino E,. Wnt signaling promotes neuronal differentiation from mesenchymal stem cells through activation of Tlx3. Stem Cells 2011; 29: 836-846.
35. Patel J, Gudehithlu KP, Dunea G, Arruda JA, Singh AK,. Foreign body-induced granulation tissue is a source of adult stem cells. Transl Res 2010; 155: 191-199.
36. Gregory CA, Harpreet S, Perry AS, Prockop DJ,. The Wnt signalling inhibitor Dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. J Biol Chem 2003; 278: 28067-28078. (Pubitemid 36900004)
37. Liu H, Fergusson MM, Castilho RM, Liu J, Cao L, Chen JK, Mailida D, Rovira II, Schimel D, Kuo CJ, Gutkind JS, Hwang PM, Finkel T,. Augmented Wnt signaling in a mammalian model of accelerated aging. Science 2007; 317: 803-806. (Pubitemid 47257917)
38. Ling L, Nurcombe V, Cool SM,. Wnt signaling controls the fate of mesenchymal stem cells. Gene 2009; 433 (1-2): 1-7.
39. Nelson WJ, Nusse R,. Convergence of Wnt, beta-catenin, and cadherin pathways. Science 2004; 303: 1483-1487. (Pubitemid 38314410)
40. Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PV, Komm BS, Javed A, van, Wijnen AJ, Stein JL, Stein GS, Lian JB,. Canonical Wnt signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem 2005; 280: 33132-33140. (Pubitemid 41397109)
41. Goldring MB, Tsuchimochi K, Ijiri K,. The control of chondrogenesis. J Cell Biochem 2006; 97: 33-44. (Pubitemid 43050970)
42. Das R, Jahr H, van, Osch GJ, Farrell E,. The role of hypoxia in bone marrow-derived mesenchymal stem cells: considerations for regenerative medicine approaches. Tissue Eng Part B Rev 2011; 16: 159-168.
43. Khan M, Akhtar S, Mohsin S, N Khan S, Riazuddin S,. Growth factor preconditioning increases the function of diabetes-impaired mesenchymal stem cells. Stem Cells Dev 2011; 20: 67-75.
44. Wisel S, Khan M, Kuppusamy ML, Mohan IK, Chacko SM, Rivera BK, Sun BC, Hideg K, Kuppusamy P,. Pharmacological preconditioning of mesenchymal stem cells with trimetazidine (1-[2,3,4-trimethoxybenzyl]piperazine) protects hypoxic cells against oxidative stress and enhances recovery of myocardial function in infarcted heart through Bcl-2 expression. J Pharmacol Exp Ther 2009; 329: 543-550.