Soluble CD146 Protein for Angiogenesis and Tissue Perfusion
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Solution Overview
Problem
Current therapeutic angiogenesis methods for treating tissue ischemia, such as using angiogenic factors like VEGF, are limited by inefficiencies and side effects, and the mobilization of endothelial progenitor cells is hindered by the low proportion of EPCs in peripheral blood and the need for large bone marrow harvests.
Innovation Solution
The use of human soluble CD146, a biologically active protein that promotes chemotactic activity and mobilization of endothelial cells, including endothelial progenitor cells, to enhance vasculogenesis and angiogenesis, either alone or in combination with other angiogenic factors and cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If angiogenic factors like VEGF are used for therapeutic angiogenesis, then new blood vessel formation is promoted, but leaky vascular lacunae and arteriovenous shunts form interfering with downstream microcirculation
Solution Approach 1:
The patent introduces soluble CD146 as an intermediary molecule that mediates endothelial cell activation and organization. Unlike VEGF which directly promotes angiogenesis but causes vascular leakage, soluble CD146 acts as a mediator that activates endothelial cells in a controlled manner, promoting proper vascular structure formation while preventing the formation of leaky vascular lacunae and arteriovenous shunts
Solution Approach 2:
The patent changes the biochemical parameters of angiogenesis by using soluble CD146 instead of VEGF. This substitution alters the activation pathway of endothelial cells, changing the quality of new blood vessel formation from leaky and disorganized (VEGF-induced) to structured and functional (soluble CD146-induced), thereby improving microcirculation while maintaining angiogenic productivity
2Productivity
If endothelial progenitor cells are transplanted to enhance neovascularization, then ischemia-induced neovascularization is augmented, but the proportion of EPCs in peripheral blood is low and large bone marrow harvests are required
Solution Approach 1:
The patent extracts and utilizes soluble CD146, a specific bioactive molecule, from the complex system of EPC transplantation. Instead of requiring large numbers of EPCs that must be harvested from bone marrow, the invention isolates and administers soluble CD146, which can mobilize and activate endogenous endothelial cells, thereby achieving neovascularization without the need for large-scale cell harvesting
Solution Approach 2:
The patent enables the body's own endothelial cells to serve the function of neovascularization when treated with soluble CD146. Rather than introducing external EPCs that require harvesting and transplantation, soluble CD146 activates the patient's existing endothelial cells to perform the angiogenic function, making the system self-service and eliminating the need for bone marrow harvest
3Productivity
If cultured EPCs are used for therapeutic angiogenesis, then neovascularization is enhanced, but the heterogeneity of recovered EPCs limits the therapeutic approach
Solution Approach 1:
The patent changes the approach from using heterogeneous EPC populations to using a defined soluble molecule (CD146). By administering soluble CD146, the therapy activates endothelial cells through a specific molecular pathway, ensuring consistent and reproducible biological effects regardless of the heterogeneity that would exist in cultured EPC populations
Data Source
AI summary
The present invention relates to compositions and methods for modulating angiogenesis in vivo, ex vivo or in vitro. More particularly, the invention relates to a soluble CD146 protein usable in the context of human therapy, as well as to corresponding antibodies. Particular forms of CD146, herein described, may be used to mobilize, in vivo or ex vivo, both mature and immature endothelial cells, as well as to increase their influence on angiogenesis. The invention also relates to compositions comprising such compounds, particularly pharmaceutical or diagnostic compositions, including kits and the like, as well as methods of therapy or diagnosis using said compounds, compositions and cells.