Francki Aleksandar, Labazzo Kristen, He Shuyang, Baum Ellen Z, Abbot Stewart E, Herzberg Uri, Hofgartner Wolfgang, Hariri Robert
Research & Development Department, Celgene Cellular Therapeutics, Warren, NJ.
Research & Development Department, Celgene Cellular Therapeutics, Warren, NJ.
J Vasc Surg. 2016 Sep;64(3):746-756.e1. doi: 10.1016/j.jvs.2015.04.387. Epub 2015 Jun 6.
Human placenta-derived adherent cells (PDACs) are a culture-expanded, undifferentiated mesenchymal-like population from full-term placental tissue and were previously shown to possess anti-inflammatory and immunomodulatory properties. PDACs (formulated as PDA-002) are in clinical trials for peripheral arterial disease with diabetic foot ulcer. In the current study, we examined their angiogenic and tissue reparative properties.
The effects of PDACs on survival and tube formation of human umbilical vein endothelial cells (HUVECs) were tested using conditioned media and noncontact coculture. Angiogenic effects were assessed in the chick chorioallantoic membrane assay. Hindlimb ischemia (HLI) was induced in mice and rats by femoral artery transection, and blood flow and blood vessel density were monitored in vivo by laser Doppler and angiography in the ischemic and control limbs. Tissue damage and regeneration in HLI were examined in histologic sections of quadriceps muscle stained with hematoxylin and eosin, and newly synthesized blood vessels were detected by indoxyl-tetrazolium staining for alkaline phosphatase.
PDACs enhanced the survival of serum-starved HUVECs and stimulated HUVEC tube formation, and in the chick chorioallantoic membrane assay, PDACs stimulated blood vessel formation. In HLI, intramuscular administration of PDACs resulted in improved blood flow and vascular density, and in quadriceps muscle, tissue regeneration and increased numbers of blood vessels were observed.
PDACs exhibited various activities consistent with angiogenesis and tissue repair, supporting the continued investigation of this cell therapy as treatment for vascular disease-related indications.
人胎盘来源的贴壁细胞（PDACs）是一种从足月胎盘组织中培养扩增的、未分化的间充质样细胞群体，先前已证明其具有抗炎和免疫调节特性。PDACs（制剂名为PDA - 002）正在用于治疗糖尿病足溃疡外周动脉疾病的临床试验。在本研究中，我们检测了它们的血管生成和组织修复特性。
使用条件培养基和非接触共培养检测PDACs对人脐静脉内皮细胞（HUVECs）存活和管腔形成的影响。在鸡胚绒毛尿囊膜试验中评估血管生成作用。通过切断股动脉在小鼠和大鼠中诱导后肢缺血（HLI），并通过激光多普勒和血管造影术在体内监测缺血肢体和对照肢体的血流及血管密度。在苏木精和伊红染色的股四头肌组织切片中检查HLI中的组织损伤和再生情况，并通过吲哚酚 - 四氮唑染色检测碱性磷酸酶以检测新合成的血管。
PDACs增强了血清饥饿的HUVECs的存活能力并刺激了HUVECs管腔形成，并且在鸡胚绒毛尿囊膜试验中，PDACs刺激了血管形成。在HLI模型中，肌肉内注射PDACs导致血流改善和血管密度增加，并且在股四头肌中，观察到组织再生和血管数量增加。
PDACs表现出与血管生成和组织修复一致的多种活性，支持继续研究这种细胞疗法用于治疗血管疾病相关适应症。
