Engineered endothelial progenitor cells that overexpress prostacyclin protect vascular cells.

Liu Q, Xi Y, Terry T, So SP, Mohite A, Zhang J, Wu G, Liu X, Cheng J, Ruan KH, Willerson JT, Dixon RA.
Source: J Cell Physiol
Publication Date: (2012)
Issue: 22(7): 2907-16
Research Area:
Cancer Research/Cell Biology
Basic Research
Cells used in publication:
Bone Marrow, Human, Unprocessed
Species: human
Tissue Origin: bone marrow
Bone marrow stroma, human
Species: human
Tissue Origin: bone marrow
Prostacyclin (PGI2) is a potent vasodilator and important mediator of vascular homeostasis; however, its clinical use is limited because of its short (<2-min) half-life. Thus, we hypothesize that the use of engineered endothelial progenitor cells (EPCs) that constitutively secrete high levels of PGI2 may overcome this limitation of PGI2 therapy. A cDNA encoding COX-1-10aa-PGIS, which links human cyclooxygenase-1 (COX-1) to prostacyclin synthase (PGIS), was delivered via nucleofection into outgrowth EPCs derived from rat bone marrow mononuclear cells. PGI2-secreting strains (PGI2-EPCs) were established by continuous subculturing of transfected cells under G418 selection. Genomic PCR, RT-PCR, and Western blot analyses confirmed the overexpression of COX-1-10aa-PGIS in PGI2-EPCs. PGI2-EPCs secreted significantly higher levels of PGI2 in vitro than native EPCs (P?