How can you tell that a cell is a stem cell? It’s really quite difficult. You can only really know by seeing whether they can regenerate tissue after being implanted into another animal. Either that or by showing that a single cell in culture can generate a line of genetically identical cells that then develop into a range of mature cell types.
In practice, scientists tend to infer that a cell is a stem cell if it tests positive for particular protein markers that are thought to be indicative of a specific type of cell. But according to new research, some of these tests are not very reliable.
Endothelial progenitor cells, or EPCs for short, are a type of stem cell that gives rise to the endothelial cells that line the walls of our blood vessels. They originate in the bone marrow and circulate in the bloodstream. Many scientists hope that EPCs can be used in new therapies to repair heart tissue, and they have already been used in clinical trials, but with limited success. A paper published in the journal Blood this week suggested that this could be because the EPCs they used were not EPCs at all.
Marianna Prokopi and colleagues at the British Heart Foundation Centre of Research Excellence at King’s College London discovered that the normal methods used to isolate EPCs in fact produce samples that are contaminated with platelets, a constituent of the blood. This is a problem because the protein markers used to identify EPCs are abundant in platelets. Platelets themselves are pretty difficult to confuse with other types of cell since they’re small and don’t have a nucleus. But it seems that proteins can be transferred from platelets into other cells.
Platelets readily disintegrate into “microparticles”, which get swallowed up by the bone marrow mononuclear cells that researchers are hoping to grow into EPCs. Thus the mononuclear cells acquire proteins from the platelets that make them look like EPCs.
Team leader Dr Manuel Mayr said: “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.”