BACKGROUND: Apolipoprotein E (ApoE) is a molecular scavenger in the blood and 
brain. Aberrant function of the molecule causes formation of protein and lipid 
deposits or "plaques" that characterize Alzheimer's disease (AD) and 
atherosclerosis. There are three human isoforms of ApoE designated epsilon2, 
epsilon3, and epsilon4. Each isoform differentially affects the structure and 
function of the protein and thus the development of disease. Homozygosity for 
ApoE epsilon4 is associated with atherosclerosis and Alzheimer's disease whereas 
ApoE epsilon2 and epsilon3 tend to be protective. Furthermore, the epsilon2 form 
may cause forms of hyperlipoproteinemia. Therefore, introduction of ApoE 
epsilon3 may be beneficial to patients that are susceptible to or suffering from 
these diseases. Mesenchymal stem cells or multipotent mesenchymal stromal cells 
(MSCs) are adult progenitor cells found in numerous tissues. They are easily 
expanded in culture and engraft into host tissues when administered 
appropriately. Furthermore, MSCs are immunosuppressive and have been reported to 
engraft as allogeneic transplants. In our previous study, mouse MSCs (mMSCs) 
were implanted into the brains of ApoE null mice, resulting in production of 
small amounts of ApoE in the brain and attenuation of cognitive deficits. 
Therefore human MSCs (hMSCs) are a promising vector for the administration of 
ApoE epsilon3 in humans.
RESULTS: Unlike mMSCs, hMSCs were found not to express ApoE in culture; 
therefore a molecular screen was performed for compounds that induce expression. 
PPARgamma agonists, neural stem cell conditioned medium, osteo-inductive media, 
dexamethasone, and adipo-inductive media (AIM) were tested. Of the conditions 
tested, only AIM or dexamethasone induced sustained secretion of ApoE in MSCs 
and the duration of secretion was only limited by the length of time MSCs could 
be sustained in culture. Upon withdrawal of the inductive stimuli, the ApoE 
secretion persisted for a further 14 days.
CONCLUSION: The data demonstrated that pre-treatment and perhaps 
co-administration of MSCs homozygous for ApoE epsilon3 and dexamethasone may 
represent a novel therapy for severe instances of AD, atherosclerosis and other 
ApoE-related diseases.