Department of Comparative Medicine, Mayo Clinic, Rochester, MN, USA.
Department of Medicine, Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Cell Transplant. 2024 Jan-Dec;33:9636897241290367. doi: 10.1177/09636897241290367.
Cardiac ventricular pressure overload affects patients with congenital heart defects and can cause cardiac insufficiency. Grafts of stem cell-derived cardiomyocytes are proposed as a complementary treatment to surgical repair of the cardiac defect, aiming to support ventricular function. Here, we report successful engraftment of human induced pluripotent stem cell-derived cardiac lineage cells into the heart of immunosuppressed rhesus macaques with a novel surgical model of right ventricular pressure overload. The human troponin+ grafts were detected in low-dose (2 × 10 cells/kg) and high-dose (10 × 10 cells/kg) treatment groups up to 12 weeks post-injection. Transplanted cells integrated and progressively matched the organization of the surrounding host myocardium. Ventricular tachycardia occurred in five out of 16 animals receiving cells, with episodes of incessant tachycardia observed in two animals; ventricular tachycardia events resolved within 19 days. Our results demonstrate that grafted cardiomyocytes mature and integrate into the myocardium of nonhuman primates modeling right ventricular pressure overload.
心脏室压过载会影响先天性心脏病患者，并可导致心脏功能不全。干细胞衍生的心肌细胞移植被提议作为心脏缺陷手术修复的补充治疗方法，旨在支持心室功能。在这里，我们报告了在右心室压力过载的新型手术模型中，将人诱导多能干细胞衍生的心脏谱系细胞成功移植到免疫抑制恒河猴的心脏中。在注射后 12 周内，低剂量（2×10 个细胞/公斤）和高剂量（10×10 个细胞/公斤）治疗组均检测到人类肌钙蛋白+移植物。移植细胞整合并逐渐与周围宿主心肌的组织相匹配。在接受细胞治疗的 16 只动物中有 5 只出现室性心动过速，其中 2 只动物出现无休止的心动过速发作；室性心动过速事件在 19 天内得到解决。我们的结果表明，移植的心肌细胞在模拟右心室压力过载的非人类灵长类动物的心肌中成熟并整合。
