COMP-angiopoietin 1 Gene Transfer Enhances Cutaneous Wound Healing: DISCUSSION continue
However, continual overexpression of VEGF has been found to result in hemangioma-type tumors , indicating that the VEGF expression or effective dose must be tightly regulated and that the expression must transiently occur only at the early stage of wound healing. Furthermore, the micro- vessels that develop from the continual over- expression of VEGF were found to be disorganized, sinusoidal and leaky because of VEFG’s additional function as a vascular permeability factor. In contrast, Ang 1 induces maturation, stabilization and remodeling of vessels and overexpression of Ang 1 does not result in vascular leakage. Therefore, Ang 1 is thought to have a wider therapeutic window and it could be a safer modality for clinical use.
As far as treatment with growth factors is concerned, naive protein treatment in the clinical setting is limited by several factors, such as their short half-lives, their inactivation by wound proteases, their poor bioavailability from the utilized vehicles and consequently the need for daily applications and high initial doses that might become toxic. An alternative approach that might overcome most of these problems is the delivery of growth factor-encoding genes. Gene therapy could overcome the short-comings of direct application of the growth factor and so promote continual production and release of the growth factor within the blood.
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In conclusion, the results of this study suggest that Ade-COMP-Ang 1 gene therapy significantly accelerates acute cutaneous wound healing by promoting angiogenesis at the site of injury. Further study using Ade-COMP-Ang 1 gene therapy in chronic wounds will be needed in the near future.
