Newsletter May 2008

iProKiTe^®-Packages

In vivo Angiogenesis Model

New: In vivo angiogenesis model based on human endothelial cell spheroids implanted in mice

We proudly present our new and unique in vivo angiogenesis assay which has just been published in Nature Methods:

Alajati A, Laib AM, Weber H, Boos AM, Bartol A, Ikenberg K, Korff T, Zentgraf H, Obodozie C, Graeser R, Christian S, Finkenzeller G, Stark GB, Héroult M, Augustin H. (2008): Spheroid-based engineering of a human vasculature in mice. 
Nature Methods 5, 439-445 (ProQinases authors in bold)

This assay allows to assess the influence of your compound on a functional human blood vessel system in vivo. It is an essential tool for testing compounds/antibodies directed against human, endothelial specific targets.

The results of the new in vivo angiogenesis model correlate very well with the results of our cellular angiogenesis assay (please see figure below).

The assay in brief:
Under certain cell culture conditions human endothelial cells aggregate spontaneously and form spheroids. Together with extracellular matrix components and angiogenic growth factors such  endothelial cell spheroids are implanted subcutaneously in SCID mice. The human endothelial cells sprout, anastomose with the mouse vasculature and form a perfused and pericyte-covered capillary network. To evaluate the effect of a compound on blood vessel formation microvessel density is determined (CD34 staining). Additional readouts like pericyte coverage or perfusion are also offered.

Fig. 1. Formation of functional human blood vessels in mice: Human endothelial cells (e.g. HUVECs) are embedded in an extracellular matrix subcutaneously in immune deficient mice where they develop a functional human vasculature. The newly formed human vessels (human CD31 and human CD34) anastomose with the mouse vasculature (arrow: mouse erythrocytes) and are covered by mouse mural cells (smooth muscle actin [SMA]).

Fig. 2. Correlation of results - Cellular Angiogenesis Assay / in vivo Angiogenesis Assay: Inhibition of endothelial cell sprouting (IC50 determination) was tested in vitro in the cellular spheroid-based angiogenesis assay for compound 1 and antibody 1 and 2. Subsequently, the same test samples were applied in the new spheroid-based in vivo angiogenesis assay. A strong reduction in vessel number in vivo was also observed for the test samples showing highest efficacy in vitro.

Recombinant Protein Kinases for Sales 

New: CDK1/CycA, MINK1, MST1, MST2, NEK7, PKC-nu and RIPK2 

Together with these 7 newcomers we have now a portfolio of 156 recombinant human protein kinases which we offer off-the-shelf. The quantities you may order range from 50 ug to real bulk amounts. Please let us know if your kinase of interest is not yet on our list of available kinases - we will do our best to change the situation.

Recombinant Protein Kinases for in vitro Testing Services

New: CDK1/CycA, DMPK, MERTK, PASK, RIPK2, S6K-beta, STK23, STK33, TEC

The 9 new kinases enlarge our panel of recombinant protein kinases for in vitro testing to 219 kinases. We offer broad profiling of single compounds as well as high-throughput screening of large libraries (32,000 data points per day).

Our ³³PanQinaseP^®P Assay is fast and very reliable. You have the choice between IC₅₀ determination, single concentration measurement or highly flexible annual data point packages. You may check here whether your kinase(s) of interest is/are available. If not, please let us know!