Pharmaceutical induction of ApoE secretion by multipotent mesenchymal stromal cells (MSCs).

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.

Pubmed ID: 18823563 RIS Download