Blood outgrowth endothelial cells overexpressing eNOS mitigate pulmonary hypertension in rats: a unique carrier cell enabling autologous cell-based gene therapy.

Blood outgrowth endothelial cells overexpressing eNOS mitigate pulmonary hypertension in rats: a unique carrier cell enabling autologous cell-based gene therapy. Transl Res. 2019 Apr 24;: Authors: Somani A, Nair SL, Milbauer LC, Zhu G, Sajja S, Solovey A, Chen Y, Hebbel RP Abstract We have investigated a unique cell type, blood outgrowth endothelial cells (BOEC), as a cell-based gene therapy approach to pulmonary hypertension. BOEC are bona fide endothelial cells, obtained from peripheral blood, that can be expanded to vast numbers, and are amenable to both cryopreservation and genetic modification. We established primary cultures of rat BOEC and genetically altered them to over-express human eNOS plus green fluorescent protein (rBOEC/eNOS) or to express GFP only (rBOEC/GFP). We gave monocrotaline to rats on day 0, and they developed severe pulmonary hypertension. As a Prevention model, we infused saline or rBOEC/GFP or rBOEC/eNOS on day 3, and then examined endpoints on day 24. The rBOEC/eNOS recipients developed elevated NOx (serum and lung) and less severe: elevation of right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary arteriolar muscularization and loss of alveolar density. As an Intervention model, we waited until day 21 to give the test infusions, and we examined endpoints on day 35. The rBOEC/eNOS recipients again developed elevated NOx and manifested the same improvements. Indeed, rBOEC/...
Source: Translational Research : the journal of laboratory and clinical medicine - Category: Laboratory Medicine Authors: Tags: Transl Res Source Type: research