Abstract
BackgroundDespite significant progress in drug treatment, the prognosis of patients with advanced pulmonary arterial hypertension (PAH) remains extremely poor. Many preclinical studies have reported the efficacy of stem cell (SC) therapy for PAH; however, this approach remains controversial. The aim of this systematic review and meta-analysis is to assess the potential efficacy of SC therapy for PAH.MethodsThe Medline, EMBASE, Cochrane Library, and Web of Science databases were searched from inception to August 12, 2018. Preclinical studies that evaluated the use of SC therapy for PAH were included. The primary outcome was pulmonary haemodynamics, as assessed by measurement of the right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and/or mean right ventricle pressure (mRVP). The secondary outcomes included the weight ratio of the right ventricle to the left ventricle plus septum (RV/LV+S), the right ventricle to body weight ratio (RV/BW), the percentage of pulmonary arteriole area index (WA), and/or the percentage of medial wall thickness of the pulmonary arteriole (WT). The quality of outcomes was evaluated using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) bias risk tool. The inverse-variance method with random-effects modelling was used to calculate pooled weighted mean differences (WMDs) and 95% CIs. Statistical analysis was performed with STATA 14.0.ResultsTwenty-eight eligible articles (722 animals) were included. SC therapy reduced the pooled WMDs (95% CIs) of RVSP, mPAP, mRVP, RV/LV+S, RV/BW, WA, and WT for animals with PAH, with values of − 14.12 (− 14.63, − 13.61), − 11.86 (− 12.35, − 11.36), − 17.33 (− 18.10, − 16.56), − 0.10 (− 0.10, − 0.09), 0.23 (0.21, 0.24), − 13.66 (− 15.71, − 11.62), and − 7.96 (− 7.99, − 7.93), respectively.ConclusionsSC therapy is effective for PAH in preclinical studies. These results may help to standardise preclinical animal studies and provide a theoretical basis for clinical trial design in the future.Systematic review registrationPROSPERO (http://www.crd.york.ac.uk/PROSPERO).
Highlights
Despite significant progress in drug treatment, the prognosis of patients with advanced pulmonary arterial hypertension (PAH) remains extremely poor
Study characteristics The number of included articles reporting right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), mean right ventricle pressure (mRVP), RV/LV+S, Right ventricle to body weight ratio (RV/BW), Pulmonary arteriole area index (WA), and Wall thickness of pulmonary arteriole (WT) was16 [14, 26, 28,29,30,31,32,33, 39, 40, 42, 45, 48,49,50], 12 [25, 30, 38, 41, 44, 47, 50], 14 [27, 34,35,36,37, 42, 50], 29 [25,26,27, 29,30,31, 33,34,35,36, 39,40,41, 43,44,45, 47, 48, 50], 16 [14, 29, 34,35,36,37, 42, 48, 50], 5 [27, 43, 44], and 23 [26, 27, 32,33,34,35,36,37, 40, 42,43,44, 49, 50], respectively
The animal model used in most studies was induced by surgical operation or by 40–60 mg/kg monocrotaline (MCT) administered intraperitoneally, subcutaneously, or via tail vein injection
Summary
Despite significant progress in drug treatment, the prognosis of patients with advanced pulmonary arterial hypertension (PAH) remains extremely poor. Many preclinical studies have reported the efficacy of stem cell (SC) therapy for PAH; this approach remains controversial. Pulmonary arterial hypertension (PAH) is a progressive chronic disease with a high mortality rate [1], and the median survival of patients with idiopathic PAH was estimated to be 2.8 years [2]. This disease is characterised by progressively increasing PAH and vascular remodelling [3], which leads to right heart failure and death [4]. There is a considerable unmet medical need in the management of PAH
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