Skip to main content
SpringerLink
Log in
Book cover

The Diabetic Foot pp 217–229Cite as

Diabetic Foot Ulcers: Effects of Hyperoxia and Stromal-Derived Factor-1α on Endothelial Progenitor Cells

  • Chapter
  • First Online:

  • 2308 Accesses

Part of the book series: Contemporary Diabetes ((CDI))

Abstract

In order for cutaneous wounds to heal in a timely manner, many requisites must be fulfilled, including infection control, resolution of inflammation, proper cell migration, differentiation, proliferation, deposition of extracellular matrix (ECM), sufficient delivery of oxygen and nutrients, wound contraction, and reepithelialization (Lazarus et al. Arch Dermatol 130:489–93, 1994). These events in turn require proper immune status, active angiogenesis/vasculogenesis, and avoidance of negative mechanical forces, such as weight bearing (Liu and Velazquez Antioxid Redox Signal 10:1869–82, 2008). Of all the above conditions, the most critical component for normal healing of full-thickness wounds is the formation of new blood vessels within the granulation tissue.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Lazarus GS, Cooper DM, Knighton DR, et al. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol. 1994;130(4):489–93.

    Article  PubMed  CAS  Google Scholar 

  2. Liu ZJ, Velazquez OC. Hyperoxia, endothelial progenitor cell mobilization, and diabetic wound healing. Antioxid Redox Signal. 2008;10(11):1869–82.

    Article  PubMed  CAS  Google Scholar 

  3. Velazquez OC. Angiogenesis and vasculogenesis: inducing the growth of new blood vessels and wound healing by stimulation of bone marrow-derived progenitor cell mobilization and homing. J Vasc Surg. 2007;45(Suppl A):A39–47.

    Article  PubMed  Google Scholar 

  4. Goldstein LJ, Gallagher KA, Bauer SM, et al. Endothelial progenitor cell release into circulation is triggered by hyperoxia-induced increases in bone marrow nitric oxide. Stem Cells. 2006;24(10):2309–18.

    Article  PubMed  CAS  Google Scholar 

  5. Tepper OM, Capla JM, Galiano RD, et al. Adult ­vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells. Blood. 2005;105(3):1068–77.

    Article  PubMed  CAS  Google Scholar 

  6. Leung PC. Diabetic foot ulcers – a comprehensive review. Surgeon. 2007;5(4):219–31.

    Article  PubMed  CAS  Google Scholar 

  7. Wu SC, Driver VR, Wrobel JS, Armstrong DG. Foot ulcers in the diabetic patient, prevention and treatment. Vasc Health Risk Manag. 2007;3(1):65–76.

    PubMed  Google Scholar 

  8. Lin CD, Allori AC, Macklin JE, et al. Topical lineage-negative progenitor-cell therapy for diabetic wounds. Plast Reconstr Surg. 2008;122(5):1341–51.

    Article  PubMed  CAS  Google Scholar 

  9. Amann B, Luedemann C, Ratei R, Schmidt-Lucke JA. Autologous bone marrow cell transplantation increases leg perfusion and reduces amputations in patients with advanced critical limb ischemia due to peripheral artery disease. Cell Transplant. 2009;18(3):371–80.

    Article  PubMed  Google Scholar 

  10. McFarlin K, Gao X, Liu YB, et al. Bone marrow-derived mesenchymal stromal cells accelerate wound healing in the rat. Wound Repair Regen. 2006;14(4):471–8.

    Article  PubMed  Google Scholar 

  11. Nambu M, Kishimoto S, Nakamura S, et al. Accelerated wound healing in healing-impaired db/db mice by autologous adipose tissue-derived stromal cells combined with atelocollagen matrix. Ann Plast Surg. 2009;62(3):317–21.

    Article  PubMed  CAS  Google Scholar 

  12. Rogers LC, Bevilacqua NJ, Armstrong DG. The use of marrow-derived stem cells to accelerate healing in chronic wounds. Int Wound J. 2008;5(1):20–5.

    Article  PubMed  Google Scholar 

  13. Kaplan RN, Psaila B, Lyden D. Niche-to-niche migration of bone-marrow-derived cells. Trends Mol Med. 2007;13(2):72–81.

    Article  PubMed  CAS  Google Scholar 

  14. Gallagher KA, Liu ZJ, Xiao M, et al. Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J Clin Invest. 2007;117(5):1249–59.

    Article  PubMed  CAS  Google Scholar 

  15. Gill M, Dias S, Hattori K, et al. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res. 2001;88(2):167–74.

    Article  PubMed  CAS  Google Scholar 

  16. Takahashi T, Kalka C, Masuda H, et al. Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999;5(4):434–8.

    Article  PubMed  CAS  Google Scholar 

  17. Griffith OW, Stuehr DJ. Nitric oxide synthases: properties and catalytic mechanism. Annu Rev Physiol. 1995;57:707–36.

    Article  PubMed  CAS  Google Scholar 

  18. Marletta MA, Hurshman AR, Rusche KM. Catalysis by nitric oxide synthase. Curr Opin Chem Biol. 1998;2(5):656–63.

    Article  PubMed  CAS  Google Scholar 

  19. Aicher A, Heeschen C, Mildner-Rihm C, et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med. 2003;9(11):1370–6.

    Article  PubMed  CAS  Google Scholar 

  20. Murohara T, Asahara T, Silver M, et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest. 1998;101(11):2567–78.

    Article  PubMed  CAS  Google Scholar 

  21. Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109(5):625–37.

    Article  PubMed  CAS  Google Scholar 

  22. Heissig B, Werb Z, Rafii S, Hattori K. Role of c-kit/Kit ligand signaling in regulating vasculogenesis. Thromb Haemost. 2003;90(4):570–6.

    PubMed  CAS  Google Scholar 

  23. Bauer SM, Goldstein LJ, Bauer RJ, Chen H, Putt M, Velazquez OC. The bone marrow-derived endothelial progenitor cell response is impaired in delayed wound healing from ischemia. J Vasc Surg. 2006;43(1):134–41.

    Article  PubMed  Google Scholar 

  24. Majka SM, Jackson KA, Kienstra KA, Majesky MW, Goodell MA, Hirschi KK. Distinct progenitor ­populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. J Clin Invest. 2003;111(1):71–9.

    PubMed  CAS  Google Scholar 

  25. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410(6829):701–5.

    Article  PubMed  CAS  Google Scholar 

  26. Sata M, Saiura A, Kunisato A, et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med. 2002;8(4):403–9.

    Article  PubMed  CAS  Google Scholar 

  27. Young PP, Hofling AA, Sands MS. VEGF increases engraftment of bone marrow-derived endothelial progenitor cells (EPCs) into vasculature of newborn murine recipients. Proc Natl Acad Sci USA. 2002;99(18):11951–6.

    Article  PubMed  CAS  Google Scholar 

  28. Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V. Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science. 2008;319(5860):195–8.

    Article  PubMed  CAS  Google Scholar 

  29. Lyden D, Hattori K, Dias S, et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med. 2001;7(11):1194–201.

    Article  PubMed  CAS  Google Scholar 

  30. Loomans CJ, de Koning EJ, Staal FJ, et al. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 2004;53(1):195–9.

    Article  PubMed  CAS  Google Scholar 

  31. Tepper OM, Galiano RD, Capla JM, et al. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation. 2002;106(22):2781–6.

    Article  PubMed  Google Scholar 

  32. Fadini GP, Miorin M, Facco M, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 2005;45(9):1449–57.

    Article  PubMed  CAS  Google Scholar 

  33. Xu B, Chibber R, Ruggiero D, Kohner E, Ritter J, Ferro A. Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products. FASEB J. 2003;17(10):1289–91.

    PubMed  CAS  Google Scholar 

  34. Roberts GP, Harding KG. Stimulation of glycosaminoglycan synthesis in cultured fibroblasts by hyperbaric oxygen. Br J Dermatol. 1994;131(5):630–3.

    Article  PubMed  CAS  Google Scholar 

  35. Jonsson K, Jensen JA, Goodson 3rd WH, et al. Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical patients. Ann Surg. 1991;214(5):605–13.

    Article  PubMed  CAS  Google Scholar 

  36. Kalani M, Jorneskog G, Naderi N, Lind F, Brismar K. Hyperbaric oxygen (HBO) therapy in treatment of diabetic foot ulcers. Long-term follow-up. J Diabetes Complications. 2002;16(2):153–8.

    Article  PubMed  Google Scholar 

  37. Hohn DC, MacKay RD, Halliday B, Hunt TK. Effect of O2 tension on microbicidal function of leukocytes in wounds and in vitro. Surg Forum. 1976;27(62):18–20.

    PubMed  CAS  Google Scholar 

  38. Uhl E, Sirsjo A, Haapaniemi T, Nilsson G, Nylander G. Hyperbaric oxygen improves wound healing in normal and ischemic skin tissue. Plast Reconstr Surg. 1994;93(4):835–41.

    Article  PubMed  CAS  Google Scholar 

  39. Sheikh AY, Gibson JJ, Rollins MD, Hopf HW, Hussain Z, Hunt TK. Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg. 2000;135(11):1293–7.

    Article  PubMed  CAS  Google Scholar 

  40. Bakker DJ. Hyperbaric oxygen therapy and the diabetic foot. Diabetes Metab Res Rev. 2000;16 Suppl 1:S55–8.

    Article  PubMed  Google Scholar 

  41. Knighton DR, Hunt TK, Scheuenstuhl H, Halliday BJ, Werb Z, Banda MJ. Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science. 1983;221(4617):1283–5.

    Article  PubMed  CAS  Google Scholar 

  42. Bonomo SR, Davidson JD, Yu Y, Xia Y, Lin X, Mustoe TA. Hyperbaric oxygen as a signal transducer: upregulation of platelet derived growth factor-beta receptor in the presence of HBO2 and PDGF. Undersea Hyperb Med. 1998;25(4):211–6.

    PubMed  CAS  Google Scholar 

  43. Duzgun AP, Satir HZ, Ozozan O, Saylam B, Kulah B, Coskun F. Effect of hyperbaric oxygen therapy on healing of diabetic foot ulcers. J Foot Ankle Surg. 2008;47(6):515–9.

    Article  PubMed  Google Scholar 

  44. Thom SR, Bhopale VM, Velazquez OC, Goldstein LJ, Thom LH, Buerk DG. Stem cell mobilization by hyperbaric oxygen. Am J Physiol. 2006;290(4):H1378–86.

    CAS  Google Scholar 

  45. Abidia A, Laden G, Kuhan G, et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. Eur J Vasc Endovasc Surg. 2003;25(6):513–8.

    Article  PubMed  CAS  Google Scholar 

  46. Faglia E, Favales F, Aldeghi A, et al. Change in major amputation rate in a center dedicated to diabetic foot care during the 1980s: prognostic determinants for major amputation. J Diabetes Complications. 1998;12(2):96–102.

    Article  PubMed  CAS  Google Scholar 

  47. Faglia E, Favales F, Aldeghi A, et al. Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer: a randomized study. Diabetes Care. 1996;19(12):1338–43.

    Article  PubMed  CAS  Google Scholar 

  48. Zamboni WA, Wong HP, Stephenson LL, Pfeifer MA. Evaluation of hyperbaric oxygen for diabetic wounds: a prospective study. Undersea Hyperb Med. 1997;24(3):175–9.

    PubMed  CAS  Google Scholar 

  49. Roeckl-Wiedmann I, Bennett M, Kranke P. Systematic review of hyperbaric oxygen in the management of chronic wounds. Br J Surg. 2005;92(1):24–32.

    Article  PubMed  CAS  Google Scholar 

  50. Kessler L, Bilbault P, Ortega F, et al. Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. Diabetes Care. 2003;26(8):2378–82.

    Article  PubMed  Google Scholar 

  51. Gordillo GM, Roy S, Khanna S, et al. Topical oxygen therapy induces vascular endothelial growth factor expression and improves closure of clinically presented chronic wounds. Clin Exp Pharmacol Physiol. 2008;35(8):957–64.

    Article  PubMed  CAS  Google Scholar 

  52. Kranke P, Bennett M, Roeckl-Wiedmann I, Debus S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev 2004(2):CD004123.

    Google Scholar 

  53. Wunderlich RP, Peters EJ, Lavery LA. Systemic hyperbaric oxygen therapy: lower-extremity wound healing and the diabetic foot. Diabetes Care. 2000;23(10):1551–5.

    Article  PubMed  CAS  Google Scholar 

  54. Lebel D, Gortzak Y, Nyska M, Katz T, Atar D, Etzion Y. Hyperbaric oxygen therapy for chronic diabetic wounds of the lower limbs – a review of the literature. Harefuah. 2007;146(3):223–7. 44–5.

    PubMed  Google Scholar 

  55. Gallagher KA, Goldstein LJ, Thom SR, Velazquez OC. Hyperbaric oxygen and bone marrow-derived endothelial progenitor cells in diabetic wound healing. Vascular. 2006;14(6):328–37.

    Article  PubMed  Google Scholar 

  56. Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10(8):858–64.

    Article  PubMed  CAS  Google Scholar 

  57. Lapidot T. Mechanism of human stem cell migration and repopulation of NOD/SCID and B2mnull NOD/SCID mice. The role of SDF-1/CXCR4 interactions. Ann N Y Acad Sci. 2001;938:83–95.

    Article  PubMed  CAS  Google Scholar 

  58. Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ. Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation. 2004;110(21):3300–5.

    Article  PubMed  Google Scholar 

  59. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study. Diabetes Care. 1998;21(5):822–7.

    Article  PubMed  CAS  Google Scholar 

  60. Hanft JR, Pollak RA, Barbul A, et al. Phase I trial on the safety of topical rhVEGF on chronic neuropathic diabetic foot ulcers. J Wound Care. 2008;17(1):30–2, 4–7.

    Google Scholar 

  61. Richard JL, Parer-Richard C, Daures JP, et al. Effect of topical basic fibroblast growth factor on the healing of chronic diabetic neuropathic ulcer of the foot. A pilot, randomized, double-blind, placebo-controlled study. Diabetes Care. 1995;18(1):64–9.

    Article  PubMed  CAS  Google Scholar 

  62. Smiell JM, Wieman TJ, Steed DL, Perry BH, Sampson AR, Schwab BH. Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies. Wound Repair Regen. 1999;7(5):335–46.

    Article  PubMed  CAS  Google Scholar 

  63. Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity ulcers. Plast Reconstr Surg. 2006;117(7 Suppl):143S–9S. discussion 50S–51S.

    Article  PubMed  CAS  Google Scholar 

  64. Fang RC, Galiano RD. A review of becaplermin gel in the treatment of diabetic neuropathic foot ulcers. Biologics. 2008;2(1):1–12.

    PubMed  CAS  Google Scholar 

  65. Galiano RD, Tepper OM, Pelo CR, et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol. 2004;164(6):1935–47.

    Article  PubMed  CAS  Google Scholar 

  66. Cruciani M, Lipsky BA, Mengoli C, de Lalla F. Granulocyte-colony stimulating factors as adjunctive therapy for diabetic foot infections. Cochrane Database Syst Rev 2009(3):CD006810.

    Google Scholar 

  67. Papanas N, Maltezos E. Becaplermin gel in the treatment of diabetic neuropathic foot ulcers. Clin Interv Aging. 2008;3(2):233–40.

    PubMed  CAS  Google Scholar 

  68. Langer A, Rogowski W. Systematic review of economic evaluations of human cell-derived wound care products for the treatment of venous leg and diabetic foot ulcers. BMC Health Serv Res. 2009;9:115.

    Article  PubMed  Google Scholar 

  69. Herdrich BJ, Lind RC, Liechty KW. Multipotent adult progenitor cells: their role in wound healing and the treatment of dermal wounds. Cytotherapy. 2008;10(6):543–50.

    Article  PubMed  CAS  Google Scholar 

  70. Assmus B, Schachinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation. 2002;106(24):3009–17.

    Article  PubMed  Google Scholar 

  71. Stamm C, Westphal B, Kleine HD, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003;361(9351):45–6.

    Article  PubMed  Google Scholar 

  72. http://www.aastrom.com/releasedetail.cfm?ReleaseID=409120. Accessed 12 May 2011.

Download references

Author information

Authors and Affiliations

  1. Division of Vascular and Endovascular Surgery, Jackson Memorial Hospital, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Ying Zhuge MD, Sharyce Gonzalez & Omaida C. Velazquez MD

Authors
  1. Ying Zhuge MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharyce Gonzalez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Omaida C. Velazquez MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Omaida C. Velazquez MD .

Editor information

Editors and Affiliations

  1. Center, Department of Surgery, Beth Israel Deaconess Medical, 1 Deaconess Road, Boston, 02215, Massachusetts, USA

    Aristidis Veves

  2. , Division of Podiatry, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, 02215, Massachusetts, USA

    John M. Giurini

  3. Center, Department of Surgery, Beth Israel Deaconess Medical, 110 Francis Street, Boston, 02215, Massachusetts, USA

    Frank W. LoGerfo

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Zhuge, Y., Gonzalez, S., Velazquez, O.C. (2012). Diabetic Foot Ulcers: Effects of Hyperoxia and Stromal-Derived Factor-1α on Endothelial Progenitor Cells. In: Veves, A., Giurini, J., LoGerfo, F. (eds) The Diabetic Foot. Contemporary Diabetes. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-791-0_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-791-0_12

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-790-3

  • Online ISBN: 978-1-61779-791-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation