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Human platelet-rich plasma- and extracellular matrix-derived peptides promote impaired cutaneous wound healing in vivo.

Demidova-Rice TN, Wolf L, Deckenback J, Hamblin MR, Herman IM - PLoS ONE (2012)

Bottom Line: Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma.In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury.Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects.

View Article: PubMed Central - PubMed

Affiliation: Graduate Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, The Center for Innovations in Wound Healing Research, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

ABSTRACT
Previous work in our laboratory has described several pro-angiogenic short peptides derived from endothelial extracellular matrices degraded by bacterial collagenase. Here we tested whether these peptides could stimulate wound healing in vivo. Our experiments demonstrated that a peptide created as combination of fragments of tenascin X and fibrillin 1 (comb1) applied into cranial dermal wounds created in mice treated with cyclophosphamide to impair wound healing, can improve the rate of wound closure. Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma. In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury. Results of in vivo experiments where comb1 and UN3 peptides were added together to cranial wounds in cyclophosphamide-treated mice leads to improvement of wound vascularization as shown by an increase of the number of blood vessels present in the wound beds. Application of the peptides markedly promotes cellular responses to injury and essentially restores wound healing dynamics to those of normal, acute wounds in the absence of cyclophosphamide impairment. Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects.

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Effects of the peptides on collagen and basement membrane deposition during wound healing.Trichrome was used to stain wounds excised at day 5 post-injury. All the animals were injected with CY prior to injury. Representative sections of wounds treated with CMC alone (A), UN3 (B), comb1 (C) or a combination of UN3 and comb1 (D). Images were taken at 5× objective lens and merged using Adobe Photoshop CS2. Arrows indicate newly deposited basement membrane. Scale bar 200 µm.
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pone-0032146-g008: Effects of the peptides on collagen and basement membrane deposition during wound healing.Trichrome was used to stain wounds excised at day 5 post-injury. All the animals were injected with CY prior to injury. Representative sections of wounds treated with CMC alone (A), UN3 (B), comb1 (C) or a combination of UN3 and comb1 (D). Images were taken at 5× objective lens and merged using Adobe Photoshop CS2. Arrows indicate newly deposited basement membrane. Scale bar 200 µm.

Mentions: In vitro studies demonstrate pro-angiogenic and pro-proliferative effects of plasma- and ECM-derived peptides, suggested that these bioactive molecules may have wound healing potential in vivo. In order to test this, we used a mouse model of impaired wound healing where Balb/c mice are pre-treated with two doses of CY at days 4 and 1 before wounding [14]. Impairment of wound healing in CY-treated mice has been observed previously [15]–[17]. However, these studies employed models of wound healing distinct from cranial dermal wounds. Therefore, first we tested whether dermal cranial wound healing would indeed be delayed in CY-treated animals. In order to estimate the degrees of healing we created and treated the wounds described in Materials and Methods, and used the grading scheme shown in Table 1 to evaluate the wound healing. Histological evaluation of the degree of wound healing revealed that CY significantly impaired cranial dermal wound healing (Figure 6A–B and Figure 7). Interestingly, this delay was more prominent at 10 days post injury and corresponded to a decrease in the number of blood vessels within the wound beds of CY treated animals compared with controls (Figures 7 and 8).


Human platelet-rich plasma- and extracellular matrix-derived peptides promote impaired cutaneous wound healing in vivo.

Demidova-Rice TN, Wolf L, Deckenback J, Hamblin MR, Herman IM - PLoS ONE (2012)

Effects of the peptides on collagen and basement membrane deposition during wound healing.Trichrome was used to stain wounds excised at day 5 post-injury. All the animals were injected with CY prior to injury. Representative sections of wounds treated with CMC alone (A), UN3 (B), comb1 (C) or a combination of UN3 and comb1 (D). Images were taken at 5× objective lens and merged using Adobe Photoshop CS2. Arrows indicate newly deposited basement membrane. Scale bar 200 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285658&req=5

pone-0032146-g008: Effects of the peptides on collagen and basement membrane deposition during wound healing.Trichrome was used to stain wounds excised at day 5 post-injury. All the animals were injected with CY prior to injury. Representative sections of wounds treated with CMC alone (A), UN3 (B), comb1 (C) or a combination of UN3 and comb1 (D). Images were taken at 5× objective lens and merged using Adobe Photoshop CS2. Arrows indicate newly deposited basement membrane. Scale bar 200 µm.
Mentions: In vitro studies demonstrate pro-angiogenic and pro-proliferative effects of plasma- and ECM-derived peptides, suggested that these bioactive molecules may have wound healing potential in vivo. In order to test this, we used a mouse model of impaired wound healing where Balb/c mice are pre-treated with two doses of CY at days 4 and 1 before wounding [14]. Impairment of wound healing in CY-treated mice has been observed previously [15]–[17]. However, these studies employed models of wound healing distinct from cranial dermal wounds. Therefore, first we tested whether dermal cranial wound healing would indeed be delayed in CY-treated animals. In order to estimate the degrees of healing we created and treated the wounds described in Materials and Methods, and used the grading scheme shown in Table 1 to evaluate the wound healing. Histological evaluation of the degree of wound healing revealed that CY significantly impaired cranial dermal wound healing (Figure 6A–B and Figure 7). Interestingly, this delay was more prominent at 10 days post injury and corresponded to a decrease in the number of blood vessels within the wound beds of CY treated animals compared with controls (Figures 7 and 8).

Bottom Line: Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma.In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury.Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects.

View Article: PubMed Central - PubMed

Affiliation: Graduate Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, The Center for Innovations in Wound Healing Research, Tufts University School of Medicine, Boston, Massachusetts, United States of America.

ABSTRACT
Previous work in our laboratory has described several pro-angiogenic short peptides derived from endothelial extracellular matrices degraded by bacterial collagenase. Here we tested whether these peptides could stimulate wound healing in vivo. Our experiments demonstrated that a peptide created as combination of fragments of tenascin X and fibrillin 1 (comb1) applied into cranial dermal wounds created in mice treated with cyclophosphamide to impair wound healing, can improve the rate of wound closure. Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma. In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury. Results of in vivo experiments where comb1 and UN3 peptides were added together to cranial wounds in cyclophosphamide-treated mice leads to improvement of wound vascularization as shown by an increase of the number of blood vessels present in the wound beds. Application of the peptides markedly promotes cellular responses to injury and essentially restores wound healing dynamics to those of normal, acute wounds in the absence of cyclophosphamide impairment. Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects.

Show MeSH
Related in: MedlinePlus