Within hours after exposure to hypoxic circumstances hMSCs start producing AGFs. Initially hypoxia does not affect hMSC proliferation and metabolic activity, but after 7 days both are decreased, compared to hMSCs cultured under ambient oxygen conditions. At the moment of implantation of a large cell seeded scaffold, usually a vascular network is lacking within the scaffold. Therefore, the cells seeded on the scaffold are exposed to hypoxic circumstances. Human mesenchymal stem cells (hMSCs) exposed to hypoxic circumstances, start to produce angiogenic factors (AGF)1 and to proliferate faster than at ambient oxygen levels2. Under severe, continued hypoxia, hMSC metabolism slows down and ultimately stops3. We hypothesise that there is a threshold oxygen level above which hMSCs at hypoxia will both produce AGF and still proliferate, and below which cells slow down their metabolism. If hMSCs are provided with oxygen levels just above this threshold, effective tissue regeneration, which requires cell proliferation and vascular ingrowth, may be accomplished.Summary
Introduction
Rat patellae were preincubated with culture medium M199 for one hour and then with either fresh culture medium or Ringer's solution, Ringer lactate, Ringer glucose, normal saline or Betadine for another hour. The rate of proteoglycan synthesis in the articular cartilage was then measured by uptake of 35SO4 for the next 16 hours. Cartilage metabolism was inhibited by all of the solutions even after a recovery time of 16 hours. The inhibition was by 5% for Ringer's solution, 10% for Ringer glucose (p <
0.01), 20% for saline and Ringer lactate (p <
0.001) and 55% for Betadine (p <
0.001). Ringer's solution is therefore the best choice for joint irrigation during arthroscopy or other procedures.
