Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: Open‐label pilot study

Abstract

Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs. In addition, our previous studies suggested that autologous EPC transplantation was feasible, safe, and might have beneficial effects on exercise capacity and pulmonary hemodynamics in adults with IPAH. Thus, we hypothesized that transplantation of EPCs would improve exercise capacity and pulmonary hemodynamics in children with IPAH. Thirteen children with IPAH received intravenous infusion of autologous EPCs. The right-sided heart catheterization and 6-MWD test were performed at baseline and at the time of 12 wk after cell infusion. At the time of 12 wk, mPAP decreased by 6.4 mmHg from 70.3 +/- 19.0 to 63.9 +/- 19.3 mmHg (p = 0.015). PVR decreased by approximately 19% from 1118 +/- 537 to 906 +/- 377 dyn s/cm(5) (p = 0.047). CO increased from 3.39 +/- 0.79 to 3.85 +/- 0.42 L/min (p = 0.048). The 6-MWD increased by 39 m from 359 +/- 82 to 399 +/- 74 m (p = 0.012). NYHA functional class also improved. There were no severe adverse events with cell infusion. The small pilot study suggested that intravenous infusion of autologous EPCs was feasible, safe, and associated with significant improvements in exercise capacity, NYHA functional class, and pulmonary hemodynamics in children with IPAH. Confirmation of these results in a randomized controlled trial are essential.

MSC Microvesicles for the Treatment of Lung Disease: A New Paradigm for Cell-Free Therapy

“…Even if MSCs maintain their differentiation potential and differentiation markers after genetic manipulation or expansion in culture, these properties do not ensure immunomodulatory and regenerative capacity. Moreover, bone marrow-derived MSCs are the best characterized and have been shown to have cytoprotective effects; yet, they have also been reported to accumulate genetic mutations after extensive expansion (9,28,81). This genomic instability may account for the unusual in vitro behavior, with early cultures growing rapidly, but eventually giving rise to heterogenous populations with variable properties that are often unable to reproduce the protective MSC effect.…”

Neo-Revascularization as the Potential Treatment for Patient Suffering from Pulmonary Arterial Hypertension (Myth or Reality)

“…Nevertheless, no define therapy exists and the long-term prognosis for these patients is poor [17]. New treatment modalities therefore are warranted to improve the patients' symptoms and survival, as a bridge to transplantation [18].…”

The Emerging Role of Stem/Progenitor Cells in Pulmonary Vascular Disease

“…This treatment was also found to be safe in children with idiopathic PAH [68]. An early phase clinical study has also been initiated (http://clinicaltrials.gov/, Identifier: NCT00469027) in Canada, to investigate the safety and potential efficacy of eNOSenhanced autologous EPCs in patients with severe PAH, refractory to all available therapies.…”