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Angiogenesis

, Volume 4, Issue 1, pp 61–70 | Cite as

CM101 stimulates cutaneous wound healing through an anti-angiogenic mechanism

  • Lillian B. Nanney
  • Barbara D. Wamil
  • Jeffrey Whitsitt
  • Nancy L. Cardwell
  • Jeffrey M. Davidson
  • He-Ping Yan
  • Carl G. Hellerqvist
Article

Abstract

CM101, an anti-pathoangiogenic polysaccharide derived from group B streptococcus, has been shown to inhibit inflammatory angiogenesis and accelerate wound healing in a mouse model and minimize scarring/gliosis following spinal cord injury. To evaluate the in vivo effects of CM101 on cutaneous wound healing in the pig, intravenously delivered CM101 or placebo vehicle was given 1 h after cutaneous wounding and again at 72 h after injury. Tissues from partial-thickness and full-thickness excisions were collected at days 4 and 7 after wounding and evaluated for a variety of standard healing parameters. Both types of CM101-treated wounds showed significantly less evidence of inflammatory angiogenesis when assessed by macroscopic photography of the wound surface, qualitative histological observations, laser doppler perfusion imaging, and quantitative morphometric analysis of microvessel area from endothelium selectively immunostained for factor VIII. Resurfacing was accelerated in partial-thickness and full-thickness excisions that received two doses of CM101 as compared to the placebo-treated excisional wounds. Neodermal thickness was increased in CM101-treated wounds at day 4 and was slightly reduced in comparison with placebo by day 7. New collagen accumulation appeared to be unaffected by the CM101 treatment. Immunohistochemical staining using a polyclonal antisera directed against the anti-pathoangiogenic CM101 target protein HP59 on day 7 indicated a strong immunoreactivity on the microvessels present in the control wounds but not in wounds of the CM101-treated animals. In summary, the immunolocalization HP59 in the microvessels of the cutaneous wound bed in control but not in CM101 treated wounds suggests that CM101 inhibits the pathologic inflammatory angiogenesis accompanying the normal granulation processes. The net biological effect of inhibited inflammatory pathoangiogenesis is a diminished, suggested and purely physiologic, microvascular bed which translates into an enhanced rate of epithelial resurfacing and therefore an overall accelerated rate of wound repair.

angiogenesis CM101 endothelium laser doppler perfusion wound healing 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Lillian B. Nanney
    • 1
    • 2
  • Barbara D. Wamil
    • 3
  • Jeffrey Whitsitt
    • 4
    • 5
  • Nancy L. Cardwell
    • 1
  • Jeffrey M. Davidson
    • 4
    • 5
  • He-Ping Yan
    • 6
  • Carl G. Hellerqvist
    • 3
  1. 1.Department of Plastic SurgeryVanderbilt School of MedicineNashvilleUSA
  2. 2.Department of Cell BiologyVanderbilt School of MedicineNashvilleUSA
  3. 3.Department of BiochemistryVanderbilt School of MedicineNashvilleUSA
  4. 4.Department of PathologyVanderbilt School of MedicineNashvilleUSA
  5. 5.Department of Veterans' AffairsVanderbilt School of MedicineNashvilleUSA
  6. 6.Department of BiologyVanderbilt School of MedicineNashvilleUSA

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