Telling a Good Batch of Mesenchymal Stem Cells from a Lousy One

If a clinician isolates mesenchymal stem cells from the fat, bone marrow, or muscles of a patient, how can they tell if these cells will be effective? Short answer – they can’t. How well the cells grow in culture and how they look is the best indicator to date, but these indicators can fool you.

Fortunately, the highly productive laboratory of Darwin Prockop from the Institute of Regenerative Medicine at Texas A & M has discovered that the expression of a gene called TSG-6 can act as an indicator for human bone marrow mesenchymal stem cell quality.

In this paper, Prockop and others examined mice that had suffered damage to the surfaces of their eyes (corneas). To mitigate the inflammation in the eye, Prockop and his colleagues applied bone marrow-derived mesenchymal stem cells, but it was clear that the stem cell batches varied remarkably in their ability to regulate inflammation.

Prockop and his group then examined the genes expressed in the different batches of bone marrow-derived mesenchymal stem cells (MSCs) in order to determine if there was a gene that was consistently expressed in the effective batches as opposed to the ineffective batches.

Fortunately, they hit pay dirt. Reverse Transcriptase-PCR assays of human MSCs for the TSG-6 gene accurately predicted their ability of a specific batch of cells to modulate inflammation during corneal injury, or damage to the body wall (sterile peritonitis), or drug-induced injury to the lung. Thus, if you want implanted MSCs to modulate inflammation, then you want cells that express TSG-6 at a high level.

However, if you want MSCs that make bone, then you do not want cells that express high levels of TSG-6 because the levels of TSG-6 mRNA were negatively correlated with their potential for osteogenic (bone cell) differentiation in culture.

Additionally, when donated MSCs from male and female donors were examined and compared, it was clear that MSCs from female donors more effectively suppressed sterile inflammation, expressed higher levels of TSG-6, and had slightly less osteogenic potential than those from male donors.

Thus, TSG-6 is a marker that can measure the ability of a batch of MSCs to suppress inflammation. It is unclear if this same gene marker equally applies to other types of MSCs, but that will hopefully become clear with further work. Also, markers that correlate with the ability of these cells to do other types of regenerative activities might also result from experiments like these.