Hypoxia – a term referring to an environment of reduced, or inadequate, oxygen supply – is not new to stem cells. In adult tissues, mesenchymal stem cells (MSCs) reside in environments of varying oxygen concentration, which is frequently below that of ambient conditions. This phenomenon has been receiving increased attention for its potential implications in regenerative medicine. A 2013 review suggested hypoxic culture conditions(2–5% O2 concentration) as being a promising alternative to current conditions for expanding MSCs.
Hypoxia is believed to increase MSC-related bone-healing processes, but the exact mechanism is not yet known. Recently, a number of papers have appeared investigating this phenomenon by analyzing osteogenesis under hypoxic conditions.
The first, from the Armed Forces Biomedical Research Institute in France, analyzed bone-healing efficiency in mouse models by subjecting them to hind-limb unloading. The authors found that bone-repair improvement occurred likely as a result of an improvement of natural bone-healing processes owing to the hypoxic conditions during remodeling, rather than the mobilization of an increased number of MSCs.
Elsewhere, researchers from the University of California Davis investigated how culture conditions (1%, 5% and 21% oxygen) affect the osteogenesis process, and found that hypoxia together with serum deprivation improved osteogenic differentiation of MSCs. The condition of 1% FBS and 5%O2 showed the highest concentration of alkaline phosphatase, which was used to characterize osteogenic efficiency.
Both of these papers are part of an increasing body of work showing how conditions far beyond what is currently considered the “norm” may shed light on improved cellular processes leading to tissue repair.