Human umbilical cord mesenchymal stem cells attenuate experimental pulmonary arterial hypertension

Abstract Background Pulmonary arterial hypertension (PAH) is characterized by the remodeling of pulmonary arteries, with an increased pulmonary arterial pressure and right ventricle (RV) overload. Until now, there is still a lack of effective treatment applied. Experimental research has reported beneficial effects of mesenchymal stem cells (MSCs) therapy in PAH. However, there are few studies on human umbilical cord mesenchymal stem cells (hUC-MSCs) transplantation in the treatment of PAH. Purpose The purpose of the present study was to observe the protective effect of hUC-MSCs against experimental PAH and the colonization of hUC-MSCs in lung tissue. Methods Sprague Dawley rats were randomly divided into three groups: control group, monocrotaline (MCT)-induced PAH group, and stem cell therapy group (PAH+ hUC-MSCs). Rats with PAH were induced by a one-time intraperitoneal injection of 60mg/kg monocrotaline (PAH and PAH+hUC-MSCs groups) at the beginning of the experiment, while a control group received saline (SAL) instead. Huc-Mscs were treated by tail vein injection twice 1 and 2 weeks later (PAH+huc-MSC group dose: 3x106/each time), Ctr and PAH groups were given the same volume of SAL in tail vein. On day 28, Right ventricular systolic pressures (RVSP) were measured by right cardiac catheterization. WT% and WA% of pulmonary arterioles were evaluated by ipp6.0 Image Analysis Software. Right ventricular hypertrophy index (RVHI) were measured by weighing method. The colonization of hUC-MSCs in lung tissue was detected by immunohistochemistry. Results The RVHI and RVSP in MCT-induced PAH group were significantly higher than those in the control group (P<0.05). Compared with the control group, the WT% and the WA% were significantly increased in MCT-induced PAH group (P<0.05). The RVHI, RVSP, WT%, and the WA% in stem cell therapy group were significantly lower than those in the MCT-induced PAH group (P<0.05). Immunohistochemical examination of lung tissue showed that the nuclear staining of the stem cell therapy group was brown, while no staining was observed in the control group and PAH group. Conclusions In MCT-induced PAH, hUC-MSCs can transplanted into the lung tissues by tail vein injection. hUC-MSCs therapy can reduced lung vascular remodeling, improved hemodynamics. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): National Natural Science Fundation of China (82060018) and Natural Science Fundation of Yunnan (202101AS070043, 202102AA31003-7).