Treatment of pulmonary arterial hypertension with circulating angiogenic cells

Abstract

Despite advances in the treatment of pulmonary arterial hypertension, a truly restorative therapy has not been achieved. Attention has been given to circulating angiogenic cells (CACs, also termed early endothelial progenitor cells) because of their ability to home to sites of vascular injury and regenerate blood vessels. We studied the efficacy of human CAC therapy in the treatment of pulmonary arterial hypertension at two different stages of disease severity. Cells were isolated from peripheral blood and administered to nude rats on day 14 ("early") or day 21 ("late") after monocrotaline injection. The control group received monocrotaline but no cell treatment. Disease progression was assessed using right heart catheterization and echocardiography at multiple time points. Survival differences, right ventricular hypertrophy (RVH), and vascular hypertrophy were analyzed at the study endpoint. Quantitative PCR was performed to evaluate cell engraftment. Treatment with human CACs either at the early or late time points did not result in increased survival, and therapy did not prevent or reduce the severity of disease compared with control. Histological analysis of RVH and vascular muscularization showed no benefit with therapy compared with control. No detectable signal was seen of human transcript in transplanted lungs at 14 or 21 days after cell transplant. In conclusion, CAC therapy was not associated with increased survival and did not result in either clinical or histological benefits. Future studies should be geared toward either earlier therapeutic time points with varying doses of unmodified CACs or genetically modified cells as a means of delivery of factors to the pulmonary arterial circulation.

Diminazene Attenuates Pulmonary Hypertension and Improves Angiogenic Progenitor Cell Functions in Experimental Models

“…There is mounting interest in testing the concept that APC therapy could be important in the treatment of PH (49)(50)(51). This view is supported by observations that circulating progenitors are dysfunctional in patients with PH (15,16).…”

High shear stress-induced pulmonary hypertension alleviated by endothelial progenitor cells independent of autophagy

“…[22] EPCs are thought to be important in maintaining vascular homeostasis by homing to sites of vascular injury and regenerating blood vessels. [23] In animal models and pilot studies in patients, EPC transplantation was proved to alleviate PH symptoms and pathological changes, providing a novel treatment strategy. Wang et al [6] reported that transplantation of autologous EPC can signifi cantly improve exercise capacity and pulmonary hemodynamics in PH patients.…”

Bone Marrow–Derived Vascular Modulatory Cells in Pulmonary Arterial Hypertension

“…51,52 Therapeutic effects of ex vivo expanded mature hematopoietic proangiogenic cells have mostly been studied in this model. 5,[13][14][15][16][17][18][52][53][54][55] In all but one of these studies, 56 administration of the proangiogenic cells before pulmonary hyper- tension onset decreased right ventricular systolic pressure and/or reduced remodeling. 44,52,54,55,57 One mechanism of benefit seems to be via increased expression of endothelial nitric oxide synthase (eNOS).…”