The University of Pittsburgh has developed a technology that enhances in vivo vasculogenic reprogramming using Tissue Nanotransfection (TNT) to deliver specific transcription factors. This innovative approach holds significant promise for diabetic wound healing and ischemic tissue regeneration. TNT is a novel technique that uses topical electrophoretic gene delivery to introduce specific transcription factors into cells. This method has been shown to induce vasculogenic fibroblasts (VF) in ischemic tissues, promoting the formation of new blood vessels. The technology leverages the upregulation of ten-eleven translocase (TET) enzymes, which play a crucial role in the vasculogenic reprogramming process. Suppressed in diabetes, TET1/2/3 play a critical role in TNT-mediated VF formation which supports de novo blood vessel development to rescue diabetic ischemic tissue.
Description
We demonstrate that the delivery of endothelial genes Etv2, Foxc2, and Fli1 plasmid DNA (EFF) in dermal fibroblasts significantly increases ischemic murine skin repair by inducing vasculogenic fibroblasts (VF) even under diabetic conditions. The approach has shown promising results in both murine in vivo and human skin ex vivo studies, highlighting its potential to revolutionize regenerative medicine and vascular biology research.
Applications
• Diabetic Wound Healing: Promotes the formation of new blood vessels to improve tissue perfusion and accelerate healing.
• Ischemic Tissue Regeneration: Enhances blood vessel formation in ischemic limbs and other tissues, offering a novel therapeutic approach.
• Regenerative Medicine: Provides a new method for tissue regeneration, improving treatments for various vascular diseases.
Advantages
• Enhanced Vasculogenic Reprogramming: The EFF delivery method significantly upregulates TET enzymes, crucial for inducing vasculogenic fibroblasts.
• Mechanistic Understanding: Increases knowledge of TET enzymes' role in vasculogenic induction.
• Potential for Better Treatments: Offers new possibilities for treating diabetic ischemic conditions and other vascular diseases.
• Novel Regeneration Method: Promotes tissue regeneration and wound healing through a unique approach.
Invention Readiness
The technology has been validated through extensive in vitro and in vivo studies, demonstrating its efficacy in generating new blood vessels to rescue wounded and ischemic tissue, even under diabetic conditions. The approach has shown promising results in both murine in vivo and human skin ex vivo studies, highlighting its potential to revolutionize regenerative medicine and vascular biology research.
IP Status
Patent pending
