Stem cell quality drops in the culture flask before transplant
Stem cell therapies promise a lot, but outcomes are notoriously variable. A growing group of researchers thinks they know part of the reason: the cells are already compromised before they are injected.
Every stem cell therapy requires cells to be expanded outside the body in a culture flask. That process takes time, and that time is not harmless. During culture, cells can enter a state in which they stop dividing but keep releasing harmful signalling molecules into their surroundings. A review covered by Fight Aging! discusses how this, and other forms of quality loss, can negatively affect outcomes of stem cell therapies.
More than just senescent cells
The authors describe how neural stem cells (brain stem cells capable of generating new nerve cells) in particular build up a damaged form of a key protective protein during culture. This damaged protein is packaged into tiny particles that the cells release into their surroundings. When those particles reach neighbouring cells, they cause damage and trigger the same harmful resting state there too. The researchers describe this as stress caused by the build-up of damaged or misshapen proteins.
Whether the same mechanism applies to other widely used stem cell types, such as mesenchymal stromal cells and induced pluripotent stem cell (iPSC)-derived products, has not yet been established. The authors call for targeted validation in those cell types.
A quality standard that does not yet exist
Current official quality standards for stem cell products check that the cells are what they should be, that they are alive, free of contamination, and genetically stable. They do not routinely check whether the cells' proteins are in good working order. The authors argue this should change. Among their recommendations: measuring how many cells have entered that harmful resting state, analysing which proteins are being released in those tiny particles, and selectively clearing out damaged proteins before transplantation.
Variability in stem cell therapy outcomes is a well-known problem. This research suggests that systematic quality control of the culture environment could be part of the answer.
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