Impact of oxygen environment on mesenchymal stem cell expansion and chondrogenic differentiation.
BACKGROUND
In vitro expansion and differentiation of mesenchymal stem cells (MSC) rely on specific environmental conditions, and investigations have demonstrated that one crucial factor is oxygen environment.


OBJECTIVE
In order to understand the impact of oxygen tension on MSC culture and chondrogenic differentiation in vitro, we developed a mathematical model of these processes and applied it in predicting optimal assays.


RESULTS
We compared ovine MSCs under physiologically low and atmospheric oxygen tension. Low oxygen tension improved their in vitro population growth as demonstrated by monoclonal expansion and colony forming assays. Moreover, it accelerated induction of the chondrogenic phenotype in subsequent three-dimensional differentiation cultures. We introduced a hybrid stochastic multiscale model of MSC organization in vitro. The model assumes that cell adaptation to non-physiological high oxygen tension reversibly changes the structure of MSC populations with respect to differentiation. In simulation series, we demonstrated that these changes profoundly affect chondrogenic potential of the populations. Our mathematical model provides a consistent explanation of our experimental findings.


CONCLUSIONS
Our approach provides new insights into organization of MSC populations in vitro. The results suggest that MSC differentiation is largely reversible and that lineage plasticity is restricted to stem cells and early progenitors. The model predicts a significant impact of short-term low oxygen treatment on MSC differentiation and optimal chondrogenic differentiation at 10-11% pO(2).
Krinner
A
A
Interdisciplinary Centre for Bioinformatics, University of Leipzig, Leipzig, Germany.
Zscharnack
M
M
Bader
A
A
Drasdo
D
D
Galle
J
J
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects*; D003198:Computer Simulation; D004058:Diffusion; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D008954:Models, Biological; D010100:Oxygen / Q000737:chemistry / Q000494:pharmacology*; D012756:Sheep
D010100:Oxygen