Efficacy of Human Embryonic Stem Cells Compared to Adipose Tissue-Derived Human Mesenchymal Stem/Stromal Cells for Repair of Murine Post-Stenotic Kidneys.
Efficacy of Human Embryonic Stem Cells Compared to Adipose Tissue-Derived Human Mesenchymal Stem/Stromal Cells for Repair of Murine Post-Stenotic Kidneys.
复制标题
与脂肪组织来源的人间充质干细胞/基质细胞相比，人胚胎干细胞修复小鼠狭窄后肾脏的功效。
DOI：
10.1007/s12015-022-10443-8
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发表时间：
2023
影响因子：
4.8
通讯作者：
Lerman,LilachO
中科院分区：
文献类型：
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作者：
Siddiqi,Sarosh;Klomjit,Nattawat;Jiang,Kai;Conley,SabenaM;Zhu,Xianyang;Saadiq,IshranM;Ferguson,ChristopherM;Tang,Hui;Lerman,Amir;Lerman,LilachO
间充质干细胞/基质细胞(MSC)的异质性和有限的复制潜能阻碍了MSC治疗的临床推广。人胚胎干细胞来源的间充质干细胞(hESC-MSCs)是从永生细胞系分化而来的，表型一致，在许多疾病模型中都显示出良好的前景。同样，脂肪组织来源的间充质干细胞(MSC(AT))具有强大的修复能力。然而，这两种细胞在疗效上的比较仍不清楚。我们随机将小鼠分为6组(每组n = 7-8)，分别接受单侧RAS或假手术(每组3只)。术后2周，将骨髓间充质干细胞(AT)S或人ESC-MSCs(5个 × 105细胞)植入小鼠的主动脉内。两周后，对小鼠进行微型核磁共振扫描，以确定肾脏血流动力学，然后采集肾脏。HESC-MSCs和MSC(AT)S在降低收缩压方面的效果相似。然而，MSC(AT)S更有力地增加了狭窄后肾脏的灌注量、氧合能力和肾小球滤过率，并更有效地减轻了肾小管损伤、纤维化和血管重构。这些观察表明，MSC(AT)在改善RAS远端肾功能障碍和组织损伤方面比hESC-MSC更有效。我们的发现强调了组织来源在选择MSCs用于治疗目的中的重要性，并强调了基于细胞的治疗肾脏疾病的实用性。
Clinical translation of mesenchymal stem/stromal cell (MSC) therapy has been impeded by the heterogenous nature and limited replicative potential of adult-derived MSCs. Human embryonic stem cell-derived MSCs (hESC-MSCs) that differentiate from immortal cell lines are phenotypically uniform and have shown promisein-vitroand in many disease models. Similarly, adipose tissue-derived MSCs (MSC(AT)) possess potent reparative properties. How these two cell types compare in efficacy, however, remains unknown. We randomly assigned mice to six groups (n = 7–8 each) that underwent unilateral RAS or a sham procedure (3 groups each). Two weeks post-operation, each mouse was administered either vehicle, MSC(AT)s, or hESC-MSCs (5 × 105cells) into the aorta. Mice were scanned with micro-MRI to determine renal hemodynamics two weeks later and kidneys then harvested. hESC-MSCs and MSC(AT)s were similarly effective at lowering systolic blood pressure. However, MSC(AT)s more robustly increased renal perfusion, oxygenation, and glomerular filtration rate in the post-stenotic kidney, and more effectively mitigated tubular injury, fibrosis, and vascular remodeling. These observations suggest that MSC(AT) are more effective than hESC-MSC in ameliorating kidney dysfunction and tissue injury distal to RAS. Our findings highlight the importance of tissue source in selection of MSCs for therapeutic purposes and underscore the utility of cell-based therapy for kidney disease.Graphical Abstract