Stem Cell Solutions: Endothelial Stem Cells, Suggested Source Of Stem Cell Therapies, Not Always What They Seem

In a result that has implications for future clinical trials, researchers have found that conventional methods for isolating mononuclear cells from blood in order to grow endothelial progenitor cells (EPCs) do not result in a pure cell sample.  Turns out they can be contaminated with markers from platelets.

Endothelial progenitor cells are a type of stem cell that have been studied for the past decade. They originate in the bone marrow and circulate in the blood. When they receive the correct signals, they are able to develop into endothelial cells, which form the lining of our blood vessels. EPCs have been suggested as a source of stem cell-based therapies to contribute to the repair of heart tissue.

Dr Manuel Mayr, from the Cardiovascular Research Division at King’s College London was aided by his research team at the College's British Heart Foundation Center of Research (BHF).  The team collected blood samples from human volunteers then isolated mononuclear cells in order to grow EPCs. They then used proteomics to examine the characteristics of these cells.

"Surprisingly, we found that conventional isolation methods used by scientists and doctors do not result in a pure cell sample," said Mayr, "because they are also contaminated with markers from another type of blood cell called platelets."

The team found that the contaminating platelets disintegrated into small membrane vesicles called ‘platelet microparticles’, which ‘bud’ from the platelets. These microparticles get swallowed up by mononuclear cells and transfer endothelial markers to them – as a result the mononuclear cells can ‘gain’ endothelial cell characteristics, and are misinterpreted as EPCs.

 
These results have implications for their use in future clinical trials and how these cells will be studied in the future by the scientific research community.

‘Many of the markers scientists currently use to identify EPCs are also present in the platelets themselves and so are not unique to EPCs. Our results suggest that cells used in some clinical trials may have been ‘masquerading’ as EPCs – but were actually a different type of cell.
 
‘We need to develop new ways of purifying EPCs and new markers to identify them that are unique to these cells. This will help us understand the properties of the cells themselves and whether EPCs are actually able to contribute to the repair of heart tissue before they are tested in trials on people. Otherwise, we cannot be certain whether potential benefits or side effects are due to stem cells or contaminating platelets.’
 
Professor Peter Weissberg, Medical Director at the BHF, concludes: ‘This important study by Dr Mayr and colleagues demonstrates that we need to change the way we do EPC research - they have provided further strong evidence that not all of the cells that we think are EPCs are cells that build new blood vessels.

Adapted from the King's College of London announcement.