Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
J Heart Lung Transplant. 2022 Jun;41(6):692-703. doi: 10.1016/j.healun.2022.02.020. Epub 2022 Mar 6.
Pulmonary arterial hypertension (PAH) remains a deadly disease, and there currently is no cure for this life-threating medical problem. The average lifespan is about 5 to 7 years after diagnosis of PAH. Therefore, a conceptual breakthrough to develop new therapeutic strategies for PAH is urgently needed. Growing evidence shows that stem cells are emerging as a novel effective treatment, but the understanding of its underlying mechanisms is still limited. This review highlights the mechanisms through which stem cells successfully reverse pulmonary vascular endothelial dysfunction, pulmonary artery smooth muscle cell over-proliferation, and mitochondrial dysfunction in PAH patients and common rodent models used in PAH research. They can modulate common underlying pathways involved in PAH, including the nitric oxide synthase, mitochondrial regulators, microRNAs and STAT3-BMPR signaling. Genetic modifications further enhance the therapeutic effects of stem cells on PAH. Clinical trials showed promising therapeutic potential of mesenchymal stem cells and endothelial progenitor cells for PAH. Potential limitations and challenges are also discussed. The current findings support the need for further investigation and validation of stem cell therapy for PAH.
肺动脉高压（PAH）仍然是一种致命的疾病，目前尚无治愈这种危及生命的医学问题的方法。PAH 诊断后，患者的平均寿命约为 5 到 7 年。因此，迫切需要在开发治疗 PAH 的新治疗策略方面取得概念上的突破。越来越多的证据表明，干细胞正在成为一种新的有效治疗方法，但对其潜在机制的理解仍然有限。这篇综述强调了干细胞成功逆转 PAH 患者肺血管内皮功能障碍、肺动脉平滑肌细胞过度增殖和线粒体功能障碍的机制，以及用于 PAH 研究的常见啮齿动物模型。它们可以调节 PAH 涉及的常见潜在途径，包括一氧化氮合酶、线粒体调节剂、microRNAs 和 STAT3-BMPR 信号通路。基因修饰进一步增强了干细胞对 PAH 的治疗效果。临床试验表明间充质干细胞和内皮祖细胞治疗 PAH 具有有希望的治疗潜力。还讨论了潜在的局限性和挑战。目前的研究结果支持进一步研究和验证干细胞治疗 PAH 的必要性。
