Amnion-Derived Adherent Cells Isolation for Angiogenesis
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Solution Overview
Problem
There is a need for additional populations of cells with angiogenic potential that are distinct from previously described placental stem cells, particularly cells that are OCT-4 negative and express specific markers such as VEGFR1/Flt-1 and VEGFR2/KDR, which can promote angiogenesis and have therapeutic applications in treating circulatory system diseases.
Innovation Solution
Isolation and characterization of amnion-derived adherent cells (AMDACs) that are OCT-4 negative and express specific markers like VEGFR1/Flt-1, VEGFR2/KDR, CD90, CD105, and CD117, which adhere to tissue culture plastic and demonstrate angiogenic properties by forming sprouts or tube-like structures in response to angiogenic factors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If placental stem cells are used for angiogenic therapy, then angiogenic potential is provided, but the cells express OCT-4 and may have unwanted pluripotent properties
Solution Approach 1:
The invention segments the placental tissue into distinct cell populations by isolating amnion-derived adherent cells (AMDACs) that are OCT-4 negative, separating the desired angiogenic function from the unwanted pluripotent properties associated with OCT-4 positive cells
Solution Approach 2:
The invention extracts and isolates a specific cell subset from placental tissue that expresses angiogenic markers (VEGFR1, VEGFR2, CD31, CD34) while explicitly excluding cells that express OCT-4, thereby obtaining a purified angiogenic cell population without pluripotent contamination
2Productivity
If stem cell populations are isolated from placenta, then cells with proliferative capacity are obtained, but differentiation into unwanted cell types may occur
Solution Approach 1:
The invention applies local quality by defining specific phenotypic characteristics for the AMDAC population (OCT-4 negative, VEGFR1 positive, VEGFR2 positive, CD31 positive, CD34 positive) that ensure the cells maintain their angiogenic identity and differentiate appropriately while retaining proliferative capacity
Solution Approach 2:
The invention changes the selection parameters from traditional OCT-4 positive stem cell markers to a new profile of OCT-4 negative cells with specific angiogenic marker expression, fundamentally altering the cell population characteristics to achieve both proliferation and stability
3Measurement precision
If traditional stem cell markers are used for cell isolation, then pluripotent cells are obtained, but cells with specific angiogenic function are not sufficiently enriched
Solution Approach 1:
The invention creates a universal cell isolation strategy that combines negative selection (OCT-4 negative) with positive selection for multiple angiogenic markers (VEGFR1, VEGFR2, CD31, CD34), achieving both high specificity for angiogenic cells and sufficient yield for therapeutic applications
Data Source
AI summary
Provided herein are novel angiogenic cells from amnion, referred to as amnion derived adherent cells, and populations of, and compositions comprising, such cells. Further provided herein are methods of obtaining such cells and methods of using the cells in the treatment of individuals.