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Creation and Transplantation of an Adipose-derived Stem Cell (ASC) Sheet in a Diabetic Wound-healing Model
Published on: August 4, 2017
Acceleration of diabetic wound healing by an angiopoietin peptide mimetic
Paul Van Slyke1, Jennifer Alami, Daniel Martin
1Molecular and Cellular Biology Research, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Insights
Vasculotide, an angiopoietin-based compound, significantly accelerates diabetic wound healing by promoting blood vessel formation and tissue repair. This novel proangiogenic therapy shows promise for treating microvascular dysfunction in diabetic patients.
Area of Science:
- Biomedical research
- Vascular biology
- Wound healing research
Background:
- Diabetic angiopathies contribute significantly to patient morbidity.
- Impaired blood glucose control leads to vascular defects, affecting conditions like diabetic retinopathy and wound healing.
- The angiopoietin family (Angs 1-4) is crucial for vascular growth and maintenance.
Purpose of the Study:
- To evaluate the efficacy of Vasculotide, a novel angiopoietin-based peptidomimetic, in treating diabetic wound healing.
- To investigate the proangiogenic mechanisms of Vasculotide in endothelial cells and in a diabetic mouse model.
Main Methods:
- Stimulation of endothelial cells (ECs) with Vasculotide to assess Tie 2 receptor activation and downstream signaling.
- Analysis of EC survival, migration, and matrix metalloproteinase 2 (MMP2) production.
- Evaluation of Vasculotide's effect on wound closure and granulation tissue formation in a diabetic mouse model (db/db mice).
Main Results:
- Vasculotide activated the Tie 2 receptor pathway, enhancing EC survival, migration, and MMP2 production.
- Combined treatment with Vasculotide and vascular endothelial growth factor (VEGF) promoted the formation of well-organized blood vessels.
- In diabetic mice, Vasculotide treatment significantly reduced wound closure times and increased granulation tissue formation.
Conclusions:
- Vasculotide demonstrates significant efficacy in accelerating diabetic wound healing.
- The compound promotes crucial biological responses for vascular repair and tissue regeneration.
- Vasculotide represents a promising therapeutic agent for diabetic microvascular dysfunction and wound healing.
Abstract:
Angiopathies are one of the leading underlying causes of morbidity in diabetic patients. Poorly managed blood glucose levels contribute to vascular defects that manifest themselves in numerous different clinical conditions, including diabetic retinopathy, nephropathy, peripheral artery disease, and compromised wound healing. The angiopoietin family (Angs 1-4) has been shown to play a critical role in the growth and maintenance of vasculature. Here we evaluate the efficacy of a new Ang-based peptidomimetic compound, Vasculotide, on diabetic-related wound healing. Stimulation of endothelial cells (ECs) with Vasculotide results in activation of the Ang receptor, Tie 2, and its associated signaling pathways. This activation promoted biological responses such as EC survival, migration, and matrix metalloproteinase 2 (MMP2) production. We show that Vasculotide alone and in combination with vascular endothelial growth factor (VEGF) results in the production of well-arborized vessels supported by myogenic cells. Using an excisional skin-wound model produced on the back of diabetic B6.Cg-m(+/+)Lepr(db)/J (db/db) mice, we found that Vasculotide-treated wounds presented with decreased wound closure times (p < 0.05) and dramatic increases in granulation tissue (p < 0.01). Although the potential of this novel proangiogenic compound in treating microvascular dysfunction is not strictly limited to topical administration, we provide mechanistic evidence as a proof of principle in support of its efficacious use in diabetic wound healing.
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