TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds

Journal of Investigative Dermatology

Volumn 134, Issue 2, 2014, Pages 526-537

  Qi, Yu ^a   Jiang, Dongsheng ^a   Sindrilaru, Anca ^a   Stegemann, Agatha ^b   Schatz, Susanne ^a   Treiber, Nicolai ^a   Rojewski, Markus ^a,c   Schrezenmeier, Hubert ^a,c   Vander Beken, Seppe ^a   Wlaschek, Meinhard ^a   Böhm, Markus ^b   Seitz, Andreas ^a   Scholz, Natalie ^a   Dürselen, Lutz ^a   Brinckmann, Jürgen ^d   Ignatius, Anita ^a   Scharffetter Kochanek, Karin ^a  

^a UNIVERSITY OF ULM   (Germany)

^b UNIVERSITY OF MÜNSTER   (Germany)

^c German Red Cross Blood Donation Service Baden Wuerttemberg Hessen   (Germany)

^d UNIVERSITY OF LÜBECK   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA3; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA STIMULATED PROTEIN 6; UNCLASSIFIED DRUG;

ACCELERATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; COCULTURE; CONTROLLED STUDY; CYTOKINE RELEASE; FULL THICKNESS SKIN GRAFT; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MACROPHAGE ACTIVATION; MESENCHYMAL STEM CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN SECRETION; SKIN FIBROSIS; SKIN INJURY; WOUND HEALING;

ANIMALS; CELL ADHESION MOLECULES; CELLS, CULTURED; COCULTURE TECHNIQUES; DISEASE MODELS, ANIMAL; FIBROSIS; HUMANS; INJECTIONS, INTRADERMAL; MACROPHAGES; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS; MICE; MICE, INBRED C57BL; SKIN; WOUND HEALING;

EID: 84892819793     PISSN: 0022202X     EISSN: 15231747     Source Type: Journal    
DOI: 10.1038/jid.2013.328     Document Type: Article

References (47)

1. Aarabi S, Bhatt KA, Shi Y et al. (2007) Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis. FASEB J 21:3250-61
2. Armstrong JR, Ferguson MW (1995) Ontogeny of the skin and the transition from scar-free to scarring phenotype during wound healing in the pouch young of a marsupial, Monodelphis domestica. Dev Biol 169:242-60
3. Bai L, Lennon DP, Eaton V et al. (2009) Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia 57:1192-203
4. Chen W, Fu X, Ge S et al. (2005) Ontogeny of expression of transforming growth factor-beta and its receptors and their possible relationship with scarless healing in human fetal skin. Wound Repair Regen 13:68-75
5. Choi H, Lee RH, Bazhanov N et al. (2011) Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-kappaB signaling in resident macrophages. Blood 118:330-8
6. Cowin AJ, Brosnan MP, Holmes TM et al. (1998) Endogenous inflammatory response to dermal wound healing in the fetal and adult mouse. Dev Dyn 212:385-93
7. Dominici M, Le Blanc K, Mueller I et al. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315-7
8. Fadok VA, Bratton DL, Konowal A et al. (1998) Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 101:890-8
9. Falanga V, Iwamoto S, Chartier M et al. (2007) Autologous bone marrowderived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. Tissue Eng 13:1299-312
10. Fekete N, Rojewski MT, Furst D et al. (2012) GMP-compliant isolation and large-scale expansion of bone marrow-derived MSC. PLoS One 7:e43255
11. Gurtner GC, Werner S, Barrandon Y et al. (2008) Wound repair and regeneration. Nature 453:314-21
12. Hinz B, Celetta G, Tomasek JJ et al. (2001) Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell 12: 2730-41
13. Hopkinson-Woolley J, Hughes D, Gordon S et al. (1994) Macrophage recruitment during limb development and wound healing in the embryonic and foetal mouse. J Cell Sci 107(Pt 5):1159-67
14. Horwitz EM, Prockop DJ, Fitzpatrick LA et al. (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309-13
15. Ignotz RA, Massague J (1986) Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 261:4337-45
16. Kokot A, Sindrilaru A, Schiller M et al. (2009) alpha-melanocyte- stimulating hormone suppresses bleomycin-induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: Melanocortin peptides as a novel treatment strategy for sclerodermä Arthritis Rheum 60:592-603
17. Le Blanc K, Ringden O (2006) Mesenchymal stem cells: Properties and role in clinical bone marrow transplantation. Curr Opin Immunol 18:586-91
18. Lee R, Pulin A, Seo M et al. (2009) Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 5:54-63
19. Lee TY, Chin GS, Kim WJ et al. (1999) Expression of transforming growth factor beta 1, 2, and 3 proteins in keloids. Ann Plast Surg 43:179-84
20. Liechty KW, Adzick NS, Crombleholme TM (2000) Diminished interleukin 6 (IL-6) production during scarless human fetal wound repair. Cytokine 12:671-6
21. Lin RY, Sullivan KM, Argenta PA et al. (1995) Exogenous transforming growth factor-beta amplifies its own expression and induces scar formation in a model of human fetal skin repair. Ann Surg 222:146-54
22. Longaker MT, Whitby DJ, Ferguson MW et al. (1994) Adult skin wounds in the fetal environment heal with scar formation. Ann Surg 219:65-72
23. Lucas T, Waisman A, Ranjan R et al. (2010) Differential roles of macrophages in diverse phases of skin repair. J Immunol 184:3964-77
24. Maggini J, Mirkin G, Bognanni I et al. (2010) Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatorylike profile. PLoS One 5:e9252
25. Martin P (1997) Wound healing-Aiming for perfect skin regeneration. Science 276:75-81
26. Mast BA, Diegelmann RF, Krummel TM et al. (1992) Scarless wound healing in the mammalian fetus. Surg Gynecol Obstet 174:441-51
27. McCallion R, Ferguson M (1997) Scar-free embryonic wound healing and the prevention of scarring following wound healing in the adult. J Theor Med 1:1-11
28. Nentwich HA, Mustafa Z, Rugg MS et al. (2002) A novel allelic variant of the human TSG-6 gene encoding an amino acid difference in the CUB module. Chromosomal localization, frequency analysis, modeling, and expression. J Biol Chem 277:15354-62
29. Occleston NL, Laverty HG, O'Kane S et al. (2008) Prevention and reduction of scarring in the skin by transforming growth factor beta 3 (TGFbeta3): From laboratory discovery to clinical pharmaceutical. J Biomater Sci Polym Ed 19:1047-63
30. Occleston NL, O'Kane S, Laverty HG et al. (2011) Discovery and development of avotermin (recombinant human transforming growth factor beta 3): A new class of prophylactic therapeutic for the improvement of scarring. Wound Repair Regen 19(Suppl 1):s38-48
31. Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8:221-33
32. Peters T, Sindrilaru A, Hinz B et al. (2005) Wound-healing defect of CD18(-/-) mice due to a decrease in TGF-beta1 and myofibroblast differentiation. EMBO J 24:3400-10
33. Prockop DJ, Oh JY (2012) Mesenchymal stem/stromal cells (MSCs): Role as guardians of inflammation. Mol Ther 20:14-20
34. Prockop DJ, Olson SD (2007) Clinical trials with adult stem/progenitor cells for tissue repair: Let's not overlook some essential precautions. Blood 109:3147-51
35. Sarrazy V, Billet F, Micallef L et al. (2011) Mechanisms of pathological scarring: Role of myofibroblasts and current developments. Wound Repair Regen 19:s10-5
36. Schrementi ME, Ferreira AM, Zender C et al. (2008) Site-specific production of TGF-beta in oral mucosal and cutaneous wounds. Wound Repair Regen 16:80-6
37. Shah M, Foreman DM, Ferguson MW (1992) Control of scarring in adult wounds by neutralising antibody to transforming growth factor beta. Lancet 339:213-4
38. Sindrilaru A, Peters T, Schymeinsky J et al. (2009) Wound healing defect of Vav3-/- mice due to impaired {beta}2-integrin-dependent macrophage phagocytosis of apoptotic neutrophils. Blood 113:5266-76
39. Sindrilaru A, Peters T, Wieschalka S et al. (2011) An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J Clin Invest 121:985-97
40. Tan KT, McGrouther DA, Day AJ et al. (2011) Characterization of hyaluronan and TSG-6 in skin scarring: Differential distribution in keloid scars, normal scars and unscarred skin. J Eur Acad Dermatol Venereol 25:317-27
41. Wang H, Peters T, Kess D et al. (2006) Activated macrophages are essential in a murine model for T cell-mediated chronic psoriasiform skin inflammation. J Clin Invest 116:2105-14
42. Wang H, Peters T, Sindrilaru A et al. (2008) TGF-beta-dependent suppressive function of Tregs requires wild-Type levels of CD18 in a mouse model of psoriasis. J Clin Invest 118:2629-39
43. Werner S, Grose R (2003) Regulation of wound healing by growth factors and cytokines. Physiol Rev 83:835-70
44. Wong VW, Sorkin M, Glotzbach JP et al. (2011) Surgical approaches to create murine models of human wound healing. J Biomed Biotechnol 2011:969618
45. Wu Y, Chen L, Scott PG et al. (2007) Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 25:2648-59
46. Young VL, Hutchison J (2009) Insights into patient and clinician concerns about scar appearance: Semiquantitative structured surveys. Plast Reconstr Surg 124:256-65
47. Zhang QZ, Su WR, Shi SH et al. (2010) Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing. Stem Cells 28:1856-68