Mesenchymal Stromal Cells from Patients with Cyanotic Congenital Heart Disease are Optimal Candidate for Cardiac Tissue Engineering

Mesenchymal Stromal Cells from Patients with Cyanotic Congenital Heart Disease are Optimal Candidate for Cardiac Tissue Engineering
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紫绀型先天性心脏病患者的间充质基质细胞是心脏组织工程的最佳候选者

DOI:
10.1016/j.biomaterials.2019.119574
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发表时间:
2020-02-01
期刊:
影响因子:
14
通讯作者:
Jiang, Shu-lin
Jiang, Shu-lin
中科院分区:
工程技术1区
文献类型:
--
作者:
Kang, Kai;Chuai, Jun-bo;Jiang, Shu-lin

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Engineered heart tissues (EHTs) are regarded as being the most promising alternative to synthetic materials, and autologous mesenchymal stem cells (MSCs) are widely used as seeding cells. However, few studies have evaluated the feasibility of using MSCs from patients with cyanotic congenital heart disease (C-CHD) as seeding cells for EHTs, in comparison with cells from patients of acyanotic congenital heart disease (A-CHD). In the present study, we cultured MSCs from A-CHD and C-CHD patients in normoxia or hypoxia conditions, and compared their pro-angiogenic, anti-apoptotic and inflammation-modulatory potentials. In vivo, we seeded the cells into collagen patches conjugated with, or without, proangiogenic cytokines, which were used to repair the right ventricular outflow tract (RVOT) of rats. The in vitro results showed that C-CHD MSCs expressed higher levels of VEGFA and VEGFR(2), and secreted more pro-angiogenic and anti-inflammatory cytokines under hypoxic conditions. On the other hand, apoptosis-related genes from C-CHD MSCs were modulated adaptably, converting these cells into an anti-apoptotic phenotype. In vivo studies demonstrated that in 4 weeks after RVOT reconstruction, cytokine-immobilized patches seeded with C-CHD MSCs exhibited preserved morphology, prolonged cell survival and enhanced angiogenesis compared to A-CHD MSCs. C-CHD MSCs that undergo "naturally hypoxic precondition" present a better cell source for EHTs, which would provide a promising individualized biomaterial for C-CHD patients.