Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL, 60208, USA.
Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Rd, Tech B382, Evanston, IL, 60208, USA.
J Cardiovasc Transl Res. 2024 Jun;17(3):558-569. doi: 10.1007/s12265-023-10452-z. Epub 2023 Oct 20.
Peripheral artery disease (PAD) is a prevalent cardiovascular disease with risks of limb loss. Our objective is to establish an autologous cell source for vascular regeneration to achieve limb salvage in PAD. Six PAD patients (age 50-80) were enrolled with their peripheral blood collected to derive vascular endothelial cells (ECs) with two different approaches: (1) endothelial progenitor cell (EPC) approach and (2) induced pluripotent stem cell (iPSC) approach. The iPSC approach successfully generated patient-specific ECs for all PAD patients, while the EPC approach did not yield any colony-forming ECs in any of the patients. The patient-derived iPSC-ECs expressed endothelial markers and exhibited endothelial functions. However, elevated inflammatory status with VCAM-1 expression was observed in the patient-derived cells. Pharmacological treatment with resveratrol resulted in patient-specific responses in cell viability and VCAM-1 expression. Our study demonstrates the potential of iPSC-ECs for autologous regenerative therapy in PAD, offering promise for personalized treatments for ischemic PAD.
外周动脉疾病（PAD）是一种常见的心血管疾病，存在肢体丧失的风险。我们的目标是建立用于血管再生的自体细胞来源，以实现 PAD 中的肢体挽救。纳入了 6 名 PAD 患者（年龄 50-80 岁），采集外周血以通过两种不同方法获得血管内皮细胞（EC）：（1）内皮祖细胞（EPC）方法和（2）诱导多能干细胞（iPSC）方法。iPSC 方法成功地为所有 PAD 患者生成了患者特异性 EC，而 EPC 方法在任何患者中均未产生任何集落形成的 EC。患者来源的 iPSC-EC 表达内皮标志物并表现出内皮功能。然而，在患者来源的细胞中观察到炎症状态升高和 VCAM-1 表达。用白藜芦醇进行药物治疗导致细胞活力和 VCAM-1 表达的患者特异性反应。我们的研究证明了 iPSC-EC 在 PAD 自体再生治疗中的潜力，为缺血性 PAD 的个体化治疗提供了希望。
