Over the last decade, there has been a lot of talk about how blood stem cells typically live in a low oxygen environment (~1 to 4%) and most of the work that researchers do is performed at normal oxygen levels (e.g., 20% of the air). However, very few researchers have studied this in a definitive manner and virtually none have kept primary cells in a completely low oxygen environment.
In a study published this week in Cell and presented here at the ISSCR meeting, Hal Broxmeyer’s lab has showed that oxygen levels have a huge influence on the number and quality of stem cells collected in experimental and clinical settings. The potential impact on stem cell transplantation protocols and stem cell banking is enormous.
In essence, the Broxmeyer lab has reported that even a brief exposure to normal oxygen levels (i.e., exposure to air) compromises both the number and quality of stem cells collected from both mouse models as well as human cord blood. If kept in completely low oxygen conditions, the number of blood stem cells recovered was increased 2-3 fold.
The first thing I was curious about was the data variability in the presentation. Whereas collecting cells in normal air was quite consistent in terms of stem and progenitor cell number and behavior, the cells obtained in low oxygen had a much larger spread. I spoke with first co-author Dr. Heather O’Leary after her talk to see if she thought this was due to length of exposure or different handling times of the cells?
“Any amount of air can skew the results,” Dr. O’Leary stated. “In some of the early experiments, when we hadn’t quite perfected keeping the stem cells in a low oxygen environment, we actually didn’t see massive differences. As we got better, the differences became greater and it turns out that even a brief exposure to normal air can change things within minutes. We also tried changing the amount of oxygen (5% instead of 3%) and found that this also impacted stem cell numbers (lower oxygen was better).”
However, doing these experiments requires a complicated setup and an important addition to this research was to show that the effect of low oxygen could be mimicked by adding a drug, cyclosporine, during cell collection. Curious to fully understand the practical application of the discovery, I asked whether cyclosporine could really replicate all of the observed effects of collecting cells in a low oxygen environment.
She replied: “We only know about the things that we’ve tested. So far, we know that the changes in stem cell function and number are replicated by just using cyclosporine. However, we really don’t know yet what impact cyclosporine may have on the other qualities of treated cells, although I would stress that the treatment is brief and we would hope that any negative consequences would be minimal.” We both agreed that a prospective clinical trial would be the best way to find out if cyclosporine treated cells were as effective as stem cells collected in the normal manner.
It is currently not practical to have a low oxygen setup in every lab or clinical facility that does a stem cell harvest, but I suspect this discovery will instigate a major push in the medical device world to develop a tool that can allow researchers and doctors to collect cells using a portable handheld device. For now, cyclosporine is probably the only potential clinical option and we don’t know that it will mimic all of the features of low oxygen.
Overall, though, this was a really exciting talk since, without making major changes to clinical practice, this discovery could lead to decreasing the shortfall of stem cell transplantation material by 2 or 3 fold. It could further help make treatments and experiments possible that were previously limited by low numbers of stem and progenitor cells.
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