Abstract
Embryoid bodies (EB) derived from pluripotent embryonic stem cells (ES) are powerful tools for different purposes. One interesting aspect is vessel development and the use for simulating angiostatic effects of drugs. Unfortunately, it is difficult to compare the impacts of different drugs. Current methods allow the description of observations, but quantifying methods are missing. To overcome that gap, we have developed a score system to transfer microscopic observations into quantifiable values. The score system summarizes different vessel characteristics within few categories and allows the comparison of drug effects in view of time and dosage. We analysed score behaviour with respect to normal vessel development as well as under presence of angiotstatic drugs. The vessel score showed a time-dependent increase under normal conditions while under presence of an angiogenesis-inhibitor the score increase was slowed, and under angiogenesis enhancing conditions the score increase was accelerated. The presented vessel development score seems to be a helpful tool to transfer microscopic observations in EB vessel development into a quantifiable and comparable value.
Highlights
Vascularization of organs and tissues is carried out by two related, but distinct processes: vasculogenesis and angiogenesis [1]
We have developed a score system to transfer microscopic observations into quantifiable values
Vasculogenesis is a process where primitive blood vessels develop from angioblast precursor cells that differentiate and assemble into cord-like vascular structures which further connect into a primary network
Summary
Vascularization of organs and tissues is carried out by two related, but distinct processes: vasculogenesis and angiogenesis [1]. Angiogenesis is a process of formation of new blood vessels from pre-existing vessels by sprouting, splitting, and remodelling of vascular network. It is a complex process including a chain of events like endothelial cell activation, growth, migration and capillary morphogenesis [2,3,4,5]. Several modulators such as inhibitors, small molecules and monoclonal antibodies have been characterised that interfere with angiogenesis Small molecules such as adenosine, 1-butyryl glycerol, prostaglandins E1 and E2 are a few examples reported for their angiogenic activity [6,7,8,9]. Monoclonal antibodies such as bevacizumab and celecoxib and small molecules such as thalidomide are already used extensively in cancer therapy for their anti-angiogenic property [10,11,12]
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