Abstract
Mesenchymal stem cells (MSCs) have been proposed for the repair of damaged tissue including bone, cartilage, and heart tissue. Upon in vivo transplantation, the MSCs encounter an ischemic microenvironment characterized by reduced oxygen (O2) tension and nutrient deprivation that may jeopardize viability of the tissue construct. The aim of this study was to assess the effects of serum deprivation and hypoxia on the MSC survival rates in vitro. As expanded MSCs are transferred from plastic to a scaffold in most tissue engineering approaches, possibly inducing loss of survival signals from matrix attachments, the effects of a scaffold shift on the MSC survival rates were also assessed. Human MSCs were exposed for 48 hours to (i) a scaffold substrate shift, (ii) serum deprivation, and (iii) O2 deprivation. MSCs were also exposed to prolonged (up to 120 hours) hypoxia associated with serum deprivation. Cell death was assessed by Live/Dead staining and image analysis. The MSC death rates were not affected by the shift to scaffold or 48-hour hypoxia, but increased with fetal bovine serum (FBS) starvation, suggesting that between the two components of ischemia, nutrient deprivation is the stronger factor. Long-term hypoxia combined with serum deprivation resulted in the complete death of MSCs (99 +/- 1%), but this rate was reduced by half when MSCs were exposed to hypoxia in the presence of 10% FBS (51 +/- 31%). These results show that MSCs are sensitive to the concurrent serum and O2 deprivation to which they are exposed when transplanted in vivo, and call for the development of new transplantation methods.
Highlights
The possibility of isolating and expanding autologous mesenchymal stem cells (MSCs) and driving them towards numerous phenotypes including chondrogenic [1,2,3,4], osteogenic [24], adipogenic [2,3,4], neural [5, 6] and cardiomyocyte [7] phenotypes, has opened new avenues for repairing lost or damaged tissues
Patients with osteoarthritis are often used in studies as a control population (2224) as bone marrow samples from such patients exhibited a maintenance of colony-forming unit fibroblasts (CFU-F) number and CFU-F osteogenic activity as assessed by alkaline phosphatase activity [25] and are of easy access
The aim of the present study was to investigate the effects of these parameters on human MSC (hMSC) survival
Summary
The possibility of isolating and expanding autologous mesenchymal stem cells (MSCs) and driving them towards numerous phenotypes including chondrogenic [1,2,3,4], osteogenic [24], adipogenic [2,3,4], neural [5, 6] and cardiomyocyte [7] phenotypes, has opened new avenues for repairing lost or damaged tissues. Transplantation of MSCs into ischemic heart causes a massive (99%) and rapid (< 4 days) cell death [7], for instance. The reasons for this high peri-transplantation cell death rate are still a matter of conjecture, but experiments in which rat neonatal cardiomyocytes grafted into a vascularized tissue survived better than cells transplanted into ischemic tissues [20] have suggested that some components of ischemia might affect the grafted cell survival rates. It seemed likely that the loss of survival signals from matrix attachments occurring during the cell detachment phase might impair hMSC survival
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