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Role of Thymic Peptides in Wound Healing

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The New Angiotherapy

Abstract

Wound repair requires the concerted action of numerous cells and factors. The inflammation, proliferation, and remodeling phases of wound healing occur in a highly coordinated cascade. Angiogenesis, the formation of new blood vessels, is one of the critical steps in the proliferative phase of wound repair (1–5). Like wound healing, angiogenesis requires cell migration, proliferation, and extracellular matrix synthesis and assembly. New vessels provide nutrients to support the repair cells, promote granulation tissue formation, and facilitate the clearance of debris. Granulation tissue is mainly composed of blood vessels that also supply the necessary oxygen to stimulate repair. Wound angiogenesis is a complex multipstep process that involves many mediators. Despite a detailed knowledge about many angiogenic factors present in the wound, little progress has been made in defining the source of these factors and the regulatory events involved in their production (1–9). Further complicating the understanding of wound angiogenesis and repair is the fact that the mechanisms and mediators involved in repair likely vary depending on the depth of the wound, type of wound (burn, trauma, etc.), and the location (muscle, skin, bone, etc.). The condition and age of the patient (diabetic, paraplegic, on steroid therapy, elderly vs infant, etc) can also determine the rate of repair and response to angiogenic factors. Furthermore, the sex of the patient and hormonal status (premenopausal, postmenopausal, etc.) may also influence the repair mechanisms and responses. Impaired wound healing particularly affects the elderly and many of the 14 million diabetics in the United States and reduced angiogenesis is often a causative agent for wound-healing problems in these patient populations.

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References

  1. DiPietro, L. A. and Nissen, N. N. (1998) Angiogenic mediators in wound healing, in Angiogenesis: Models, Modulators and Clinical Applications ( Maragoudakis, M. E., Ed.), Plenum Press, NY.

    Google Scholar 

  2. Coleville-Nash, P. R. and Willoughby, D. A. (1997) Growth factors in angiogenesis: current interest and therapeutic potential. Mol. Med. Today January, 14–23.

    Google Scholar 

  3. Bennett, N. T. and Schultz, G. S. (1993) Growth factors and wound healing: Part II. role in normal and chronic wound healing. Am. J. Surg. 166, 74–81.

    Article  PubMed  CAS  Google Scholar 

  4. Arnold, F., West, D. C., Schofield, P. F., and Kumar, S. (1987) Angiogenic activity in human wound fluid. Int. J. Microcirc. Clin. Exp. 5, 381–386.

    PubMed  CAS  Google Scholar 

  5. Dvonch, V. M., Murphy, R. J., Matsuoka, J., and Grotendorst, G. (1992) Changes in growth factor levels in human wound fluid. Surgery 112, 18–23.

    Google Scholar 

  6. Hunt, T. K., Knighton, D. R., Thakral, K. K., Goodson, W. H., III, and Andrew, W. S. (1984) Studies on inflammation and wound healing:angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages. Surgery 96, 48–54.

    Google Scholar 

  7. Rapollee, D. A., Mark, D., Banda, M. J., and Werb, Z. (1988) Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by RNA phenotyping. Science 241, 708–712.

    Google Scholar 

  8. Poverini, P. and DiPietro, L. A. (1992) Role of macrophages in the regulation of physiological and patholgoical angiogenesis, in Angiogenesis in Health and Disease ( Maragoudkis, M. E., ed.), Plenum Press, NY pp. 43–53.

    Chapter  Google Scholar 

  9. Liebovich, S. J. and Ross, R. (1974) The role of the macrophage in wound repair: a study with hydrocortisone and antimacrophage serum. Am. J. Pathol. 78, 81–84.

    Google Scholar 

  10. Danon, D., Madjar, J., Edinov, E., Knyszynski, A., Brill, S., Dimanmtishtein, L., and Shinar, E (1997) Treament of human ulcers by application of macrophages prepared from a blood unit. Exp. Gerontol. 32, 633–641.

    Article  PubMed  CAS  Google Scholar 

  11. Ferrara, N., Houck, K., Jakeman L., and Leung, D. (1992) Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr. Rev. 13, 18–23.

    PubMed  CAS  Google Scholar 

  12. Gospodarowicz, D., Ferrara, N., Schweiger, L., and Neufeld, G. (1987) Structural characterization and biological functions of fibroblast growth factor. Endocrinol. Rev. 8 95–114.

    Article  CAS  Google Scholar 

  13. Xu, X., Weinstein, M., Li, C., Naski, M., Cohen, R. I., Ornitz, D.M., Leder, P., and Deng, C. (1998). Fibroblast frowth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development 125, 753–765.

    Google Scholar 

  14. Knighton, D. R., Phillips, G. D., and Fiegel, V. D. (1990) Wound healing angiogenesis:indirect stimulation by basic fibroblast growth factor. J. Trauma 30, 134–144.

    Article  Google Scholar 

  15. Nissen, N. N., Poverini, P. D., Gamelli, R. L., and DiPietro, L. A. (1996) Basic fibroblast growth factor mediates angiogenic activity in early surgical wounds. Surgery 119, 457–465.

    Article  PubMed  CAS  Google Scholar 

  16. Okumura, M. Okuda,T., Nakamura, T., and Yajima, M. (1996) Acceleration of wound healing in diabetic mice by basic fibroblast growth factor. Biol. Pharm. Bull. 19 530–535.

    Google Scholar 

  17. Greenhalgh, D., G., Sprugel, K. H., Murray, M. J., and Ross, R. (1990) PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am. J. Pathol. 136, 1235–1245.

    Google Scholar 

  18. Malinda, K. M., Goldstein, A. L., and Kleinman, H. K. (1997) Thymosin 134 stimulates directional migration of human umbilical vein endothelial cells. J. Immunol. 11, 474–481.

    CAS  Google Scholar 

  19. Knighton, D. R., Ciresi, K., Fiegel, V. D., Schuermerth, S., Butler, E., and Cerra, F. (1990) Stimulators of repair in chronic, non healing, cutaneous ulcers using platelet-derived wound healing formula. Surg. Gynecol. Obstet. 170, 50–60.

    Google Scholar 

  20. Szabo, S. (1994) Accelerated wound healing of duodenal ulcers by oral administration of a mutein of basic fibroblast growth factor. Gastroenterology 106, 1106–1111.

    PubMed  CAS  Google Scholar 

  21. Arnold, F., West, D., and Kumar, S. (1987) Wound healing: the effect of macrophage and tumor derived angiogenic factors on skin graft vascularization. Br. J. Exp. Pathol. 68, 569–574.

    PubMed  CAS  Google Scholar 

  22. Eppley, B. L., Doucet, M., Connolly, D. T., and Feder, J. (1988) Enhancement of angiogenesis by bFGF in mandibular bone graft healing in the rabbit. J. Oral Maxillo. Fac. Surg. 46, 391–398.

    Google Scholar 

  23. Joyce, M. E., Roberts, A. B., Sporn, M. B., and Bolander, M. E. (1990) Transforming growth factor beta and initiation of chondrogenesis and osteogenesis in the femur. J. Cell Biol. 110, 2195–2207.

    Google Scholar 

  24. Kurita, Y., Tsuboi, R., Uiki, R., Rifkin, D. B., and Ogawa, H. (1992) Immunohistomchemical localization of basic fibroblast growth factor in wound healing site of mouse skin. Arch. Dermatol. Res. 284, 193–197.

    Google Scholar 

  25. Bashkin, P, Doctrow, S., Klagsbrun, M., Svahn, C. M., Folkman, J., and Vlodaysky, I. (1989) Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules. Biochemistry 28, 1737–1743.

    Article  PubMed  CAS  Google Scholar 

  26. Uhl, E., Rosken, F., and Messmer, K. (1997) Transdermal administration of platelet-derived growth factor for improved wound healing in local ischemia and diabetes mellitus. Langenbecks Arch. Chir. Suppl. Kongress 114, 705–708.

    Google Scholar 

  27. Malchereck, P. Schultz, G., Wingren, U., and Franzen, L. (1994) Formation of healing tissue and angiogenesis in repair of connective tissue stimulated by epidermal growth factor. Scand. J. Plast. Reconstr. Hand Surg. 28 1–7.

    Google Scholar 

  28. Brown, L. F., Yeo, K. T., Berse, B., Yeo, T. K., Senger, D. R., Dvorak, H. F., and Van Der Water, L. (1992) Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J. Exp. Med. 176, 1375–1381.

    Article  PubMed  CAS  Google Scholar 

  29. Nissen, N. N., Poverini, P. J., Koch, A. E., Volin, M. V., Gamelli, R. L., and DiPietro, L. A. (1998) Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am. J. Pathol. 152, 1445–1452.

    PubMed  CAS  Google Scholar 

  30. Chegni, N. (1997) The role of growth factors in peritoneal healing; transforming growth factor beta. Eur. J. Surg. 577, 17–23.

    Google Scholar 

  31. Grant, D. S., Kinsella, J. L., Kibbey, M. C., LaFlamme, S., Burbelo, P. D., Goldstein, A. L., and Kleinman, H. K. (1995) Matrigel induces thymosin beta 4 in differentiating endothelial cells. J. Cell Sci. 108, 3685–3694.

    Google Scholar 

  32. Malinda, K. M., Sidhu, G. S., Banaudha, K. K., Gaddipati, J. P., Maheshwari, R. K., Goldstein, A. L., and Kleinman, H. K. (1998) Thymosin alpha 1 stimulates endothelial cell migration, angiogenesis and wound healing. J. Immunol. 160, 1001–1006.

    PubMed  CAS  Google Scholar 

  33. Oates, K. and Goldstein, A.L. (1995) Thymosin, in Biological Therapy of Cancer (DeVita, V. T., Hellman, S., and Rosenberg, R. A., Eds.), J. B. Lippincott Co, PA, pp. 841–853.

    Google Scholar 

  34. Yokoi, H. Saitoh, T., Nakazawa, U., and Ohno, H. (1996) An immunoradiometric assay for thymosin al. J. Immunoassay 17 85–88.

    Google Scholar 

  35. Clark, A. F. (1996) Wound repair: an overview and general considerations, in The Molecular and Cellular Biology of Wound Repair ( Clark, A. F., ed.), Plenum Press, New York, pp. 1–50.

    Google Scholar 

  36. Danon, D. Kovatch, M. A ., and Rogh, G. S. (1989) Promotion of wound repair in old mice by local injections of macrophages. PNAS 86 2018–2020.

    Google Scholar 

  37. Stout, A. J., Gusser, I., and Thompson, W., D. (1993) Inhibition of wound healing in mice by local interferon ad3 injection. Int. J. Pathol. 74, 79–85.

    Google Scholar 

  38. Folkman, J. and Shing, Y. (1992) Angiogenesis. J. Biol. Chem. 267, 10,931–10, 934.

    Google Scholar 

  39. Sephel, G. C., Kennedy, R., and Kudav, S. (1996) Expression of capillary basement membrane components during sequential phases of wound angiogenesis. Matrix Biol. 15, 263–279.

    Google Scholar 

  40. Moscatelli, D. and Rifkin, D. B. (1988) Membrane and matrix localization of proteases: a common theme in tumor cell invasion and angiogenesis. Biochem. Biophys. Acta 948, 67–85.

    Google Scholar 

  41. Vukecivic, S., Kleinman, H. K., Luyten, F. P., Roberts, A. B., Roche, N. S., and Reddi, A. H. (1992) Identification of multiple active growth factors in basement membrane matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components. Exp. Cell Res. 202, 1–8.

    Article  Google Scholar 

  42. Grant, D. S., Kinsella, J. L., Fridman, R., Auerbach, R., Piasecki, B. A., Yamada, Y., (1992) Interaction of endothelial cells with a laminin A chain peptide (SIKVAV) in vitro and induction of angiogenic behavior in vivo. J. Cell. Physiol. 153, 614–625.

    Google Scholar 

  43. Haralabopoulos, G. C., Grand, D. S., Kleinman, H K, Lelkes, P.I., Papaionnou, S. P., and Maragoudakis, M. E. (1994) Inhibitors of basement membrane collagen synthesis prevent endothelial cell alignment in matrigel in vitro and angiogenesis in vivo. Lab. Invest. 71, 575–582.

    Google Scholar 

  44. Kubota, Y., Kleinman, H. K., Martin, G. R., and Lawley, T. J. (1988) Role of laminin and basement membrane in the differentiation of human endothelial cells into capillary-like structures. J. Cell Biol. 170, 1589–1597.

    Article  Google Scholar 

  45. Safer, D. and Nachamias, V. T. (1994) Beta thymosins as actin binding proteins. BioEssays 16 473–479.

    Google Scholar 

  46. Bao, L., Loda, M., Jamey, P. A., Stewart, R., Anand-Apte, B., and Zetter, B. R. (1996) Thymosin beta 15 : a novel regulator of tumor cell motility upregulated in metastatic prostate cancer. Nature Med. 2,1322–1328.

    Google Scholar 

  47. Goldstein, A. L. (1994) Clinical applications of thymosin al. Cancer Invest. 12, 545–560.

    Article  PubMed  CAS  Google Scholar 

  48. Robson, M. C., Mustoes, T. A., Hunt, T. K. (1998) The future of recombinant growth factors in wound healing. Am. J. Surg. 176, 80S - 82S.

    Article  PubMed  CAS  Google Scholar 

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Kleinman, H.K., Grant, D.S., Malinda, K.M. (2002). Role of Thymic Peptides in Wound Healing. In: Fan, TP.D., Kohn, E.C. (eds) The New Angiotherapy. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-126-8_12

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  • DOI: https://doi.org/10.1007/978-1-59259-126-8_12

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9657-4

  • Online ISBN: 978-1-59259-126-8

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