Heart Research Institute, Newtown, NSW, Australia.
Sydney Medical School, University of Sydney, Camperdown, NSW, Australia.
PLoS One. 2021 Aug 10;16(8):e0255075. doi: 10.1371/journal.pone.0255075. eCollection 2021.
Induced endothelial cells (iECs) generated from neonatal fibroblasts via transdifferentiation have been shown to have pro-angiogenic properties and are a potential therapy for peripheral arterial disease (PAD). It is unknown if iECs can be generated from fibroblasts collected from PAD patients and whether these cells are pro-angiogenic. In this study fibroblasts were collected from four PAD patients undergoing carotid endarterectomies. These cells, and neonatal fibroblasts, were transdifferentiated into iECs using modified mRNA. Endothelial phenotype and pro-angiogenic cytokine secretion were investigated. NOD-SCID mice underwent surgery to induce hindlimb ischaemia in a murine model of PAD. Mice received intramuscular injections with either control vehicle, or 1 × 106 neonatal-derived or 1 × 106 patient-derived iECs. Recovery in perfusion to the affected limb was measured using laser Doppler scanning. Perfusion recovery was enhanced in mice treated with neonatal-derived iECs and in two of the three patient-derived iEC lines investigated in vivo. Patient-derived iECs can be successfully generated from PAD patients and for specific patients display comparable pro-angiogenic properties to neonatal-derived iECs.
通过转分化从新生儿成纤维细胞中产生的诱导内皮细胞（iECs）已被证明具有促血管生成特性，是治疗外周动脉疾病（PAD）的潜在方法。目前尚不清楚是否可以从 PAD 患者的成纤维细胞中产生 iECs，以及这些细胞是否具有促血管生成作用。在这项研究中，从 4 名接受颈动脉内膜切除术的 PAD 患者中收集了成纤维细胞。使用改良的 mRNA 将这些细胞和新生儿成纤维细胞转分化为 iECs。研究了内皮表型和促血管生成细胞因子的分泌。NOD-SCID 小鼠接受手术，在 PAD 的小鼠模型中诱导后肢缺血。小鼠接受肌肉内注射对照物、1×106 个新生来源的或 1×106 个患者来源的 iECs。使用激光多普勒扫描测量受影响肢体的灌注恢复情况。接受新生来源的 iECs 治疗的小鼠和体内研究的 3 种患者来源的 iEC 系中的 2 种的灌注恢复得到增强。可以从 PAD 患者中成功产生患者来源的 iECs，并且对于特定的患者，它们显示出与新生来源的 iECs 相当的促血管生成特性。
