Author + information
- Seungbum Choi,
- Seyeon Oh,
- Sehyun Chae,
- Jeongsik Moon,
- Kyung-Hee Kim,
- Bo Ram Choi,
- Myeong Gun Kim,
- Sihun Kim,
- Minsu Kim,
- Youngwoo Jang,
- Daehee Hwang,
- Kyunghee Byun and
- Wook-Jin Chung
Background: Administration of human adipose tissue, bone marrow, or umbilical cord blood-derived mesenchymal stem cell (AD, BD, or UCB-MSC) has shown promising clinical outcomes in animal models of pulmonary arterial hypertension (PAH), however which source of MSC has the greatest therapeutic potential has not been thoroughly investigated. This study aimed to compare the effects of three MSCs on RV failure, vascular remodeling, inflammation, and genes involved in both current and future potential therapeutic target pathways.
Methods: 1×106 MSCs were intravenously administered into monocrotaline-induced PAH rats. At 1, 3, 5, and 7 days post-administration, engrafted MSC survival in lungs was examined by measuring the mRNA level of three human MSC markers, CD29, CD44, and CD90. Two weeks after MSC administration, (1) RV hemodynamics were determined by echocardiography, (2) pulmonary arterial media wall thickness and perivascular fibrosis by histological assessment, (3) cell proliferation and inflammation by immune-staining, and (4) gene expression by microarray.
Results: CD29, CD44, and CD90 levels in UCB-MSC treated group remains highest until 5 days post-MSC treatment. Tricuspid regurgitation pressure gradient and annular plane systolic excursion were improved by UCB-MSC treatment. Increased medial wall thickness, fibrosis, and cell proliferation were similarly attenuated by all the three MSCs. Expression of genes involved in prostacyclin, nitric oxide, endothelin, and apelin pathways was positively influenced by UCB-MSC. Increase of IBA1, Cd11c, Il-1β, Tnf-α, and Tgf-β levels were significantly attenuated by UCB-MSC, and decrease of arginase I was reversed by MSCs.
Conclusions: Compared with AD- and BD-MSC, UCB-MSC has greater positive influences on engrafted cell survival, RV hemodynamics, vasodilation, and vasoconstriction. In particular, UCB-MSC upregulates key genes in prostacyclin and apelin pathways, which may lead to the reduction of inflammation and induction of T2 macrophage. Combination of MSC-based therapy with conventional therapies may improve clinical outcomes. We propose that UCB may be the best source for MSC-based PAH treatment.
Moderated Poster Contributions
Congenital Heart Disease and Pulmonary Hypertension Moderated Poster Theater, Poster Hall, Hall C
Saturday, March 18, 2017, 10:15 a.m.-10:25 a.m.
Session Title: Bridge From the Basics: Translational Research in Pulmonary Hypertension
Abstract Category: 35. Pulmonary Hypertension and Pulmonary Thrombo-embolic Disease
Presentation Number: 1208M-07
- 2017 American College of Cardiology Foundation