Energy Metabolism Analysis of Three Different Mesenchymal Stem Cell Populations of Umbilical Cord Under Normal and Pathologic Conditions
Energy Metabolism Analysis of Three Different Mesenchymal Stem Cell Populations of Umbilical Cord Under Normal and Pathologic Conditions
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DOI：
10.1007/s12015-020-09967-8
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发表时间：
2020-03-17
影响因子：
4.8
通讯作者：
Borlongan, Cesar V.
中科院分区：
文献类型：
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作者：
Russo, Eleonora;Lee, Jea-Young;Borlongan, Cesar V.
人脐带间充质干细胞(Huc-MSCs)因其具有多向分化潜能、免疫调节和抗炎特性，以及后勤收集优势而无需伦理考虑，是再生医学治疗活性细胞的关键来源。然而，目前尚不清楚来自不同脐带间隔的间充质干细胞在治疗上是否优于其他干细胞。本研究从Huc的Wharton凝胶(WJ-MSCs)、血管周围区(PV-MSCs)和脐带衬里(CL-MSCs)中分离出MSCs。WJ-、PV-和CL-MSCs分别表达间充质标志物(CD90、CD73)、干性标志物(OCT4)、内皮细胞黏附分子标志物(CD146)和单核/巨噬细胞标志物(CD14)。中风和再灌流期间缺乏氧气和葡萄糖的直接后果是线粒体功能受损，导致细胞死亡。线粒体转移的新发现为补充健康的线粒体作为治疗中风的策略提供了基础。细胞能量表型和Mito应激试验检测了三个MSC群体在环境和OGD细胞培养条件下的能量代谢谱和线粒体功能。PV-MSCs的线粒体活性最高。CL-MSCs受OGD/R状态影响最小，提示其在缺血环境中存活良好。在本研究中，UC的MSC群体在正常和低氧条件下具有相似的代谢能力和良好的存活能力，这表明它们有可能作为基于线粒体的干细胞治疗中风和其他缺血性疾病的可移植细胞。
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a pivotal source of therapeutically active cells for regenerative medicine due to their multipotent differentiation potential, immunomodulatory and anti-inflammatory proprieties, as well as logistical collection advantages without ethical concerns. However, it remains poorly understood whether MSCs from different compartments of the human umbilical cord are therapeutically superior than others. In this study, MSCs were isolated from Wharton's jelly (WJ-MSCs), perivascular region (PV-MSCs) and cord lining (CL-MSCs) of hUC. These cells expressed the mesenchymal markers (CD90, CD73), stemness marker (OCT4), endothelial cell adhesion molecular marker (CD146), and the monocyte/macrophage marker (CD14) found within the MSC population implicated as a key regulator of inflammatory responses to hypoxia, was displayed by WJ-, PV-, and CL-MSCs respectively. A direct consequence of oxygen and glucose deprivation during stroke and reperfusion is impaired mitochondrial function that contributes to cellular death. Emerging findings of mitochondria transfer provide the basis for the replenishment of healthy mitochondria as a strategy for the treatment of stroke. Cell Energy Phenotype and Mito Stress tests were performed the energy metabolic profile of the three MSC populations and their mitochondrial function in both ambient and OGD cell culture conditions. PV-MSCs showed the highest mitochondrial activity. CL-MSCs were the least affected by OGD/R condition, suggesting their robust survival in ischemic environment. In this study, MSC populations in UC possess comparable metabolic capacities and good survival under normal and hypoxic conditions suggesting their potential as transplantable cells for mitochondrial-based stem cell therapy in stroke and other ischemic diseases.