ANGIOGENESIS SERVICES
 
 
 OVERVIEW
 

As tumors grow they have increased requirements for oxygen and nutrients. To induce the formation of new blood vessels to meet this need (angiogenesis), tumors secrete a number of growth factors such as VEGF and FGFb.  The blood vessels that form provide the added oxygen and nutrients tumors need for continuous growth as well as an avenue for the metastatic spread of the tumor.  Because of this, angiogenesis has become a prime target in the fight against cancer.

 
 IMPROVED MATRIGEL PLUG ASSAY
 

Matrigel is a gelatinous material derived from mouse tumor cells that is commonly used in vitro and in vivo as a substrate for cells.  When pro- angiogenic agents are also added to the matrigel and it is injected into the subcutaneous space of an animal, new blood vessels invade the matrigel, similar to vessel formation in tumors.  This is the basis of an assay referred to as the “matrigel plug” assay.  The matrigel can be harvested and the new vessel formation in the plug can be assessed.  The difficulty with the traditional matrigel plug assay is that the matrigel disperses easily in the subcutaneous tissue and does not form a tight solid mass.  MIR has developed methods that minimizes this dispersion.

This figure shows one method of quantifying the angiogenesis data generated from a matrigel plug assay and how treatment groups can be directly compare to control groups. MIR Preclinical Services has optimized this assay of angiogenesis to minimize matrigel loss and subcutaneous spread to yield less variable results than the standard matrigel plug assay. The low p value indicates the strong statistical difference between treated and control groups using this assay.

Matrigel Angiogenic Factors (VEGF/FGFb/Heparin)
Mann- Whitney Rank  Sum Test, P value <0.001

 

Control
Sutent PO QDx7 @ 40mg/kg
This image shows the invasion of endothelial tissue into the matrigel plug from the subcutaneous environment. MIR can also perform histology and imunohistochemistry on plugs that are produced according to a clients needs.
This image shows the invasion of endothelial tissue into the matrigel plug from the subcutaneous environment. MIR can also perform histology and imunohistochemistry on plugs that are produced according to a clients needs.
This image shows demonstrates how sutent is able to prevent the invasion of endothelial tissue into the matrigel plug from the subcutaneous environment. MIR can also perform histology and imunohistochemistry on plugs that are produced according to clients needs.
This image shows demonstrates how sutent is able to prevent the invasion of endothelial tissue into the matrigel plug from the subcutaneous environment. MIR can also perform histology and imunohistochemistry on plugs that are produced according to clients needs.
ADDITIONAL CAPABILITIES
 
 HISTOLOGY
 

MIR offers histology and immunohistochemistry services to determine vessel formation in tumors using endothelial cell markers such as CD31 or Factor 8.  Blood vessels can then be quantified by counting the number of vessels present within a defined frame of view over a number of different slices throughout the depth of the tumor.  Other methods are also under development. 
 
 DYNAMIC CONTRAST ENHANCED (DCE) MRI
 

DCE MRI is a method for the quantification of the effect of anti-angiogenic or vascular disrupting agents. DCE can be used to assess anti-angiogenesis activity in preclinical studies and can be directly translated as a biomarker in clinical trials. DCE involves imaging of gadolinium uptake into the interstitial space for the quantification of vascular permeability, vascular surface area and blood flow. Color overlay vascular maps showing the permeability of tissues based on the uptake and transport of contrast agent can be used to visualize vascular response.

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 FUTURE DIRECTIONS
 

The matrigel plug assay induces angiogenesis in response to exogenously added growth factors. We are also currently developing models of angiogenesis that are driven by endogenously secreted trophic and angiogenic factors.
 
 
Angiogenesis Flier
800 Technology Drive• Ann Arbor, Michigan 48108
Phone: 734.821.1063 Fax:734.821.1066
   
updated:  4/30/08