Podocytes are highly differentiated epithelial cells that are crucial for maintaining the glomerular filtration barrier in the kidney. Podocyte injury followed by depletion is the major cause of pathological progression of kidney diseases. Although cell therapy has been considered a promising alternative approach to kidney transplantation for the treatment of kidney injury, the resultant therapeutic efficacy in terms of improved renal function is limited, possibly owing to significant loss of engrafted cells. Herein, hybrid three‐dimensional (3D) cell spheroids composed of podocytes, mesenchymal stem cells, and vascular endothelial cells were designed to mimic the glomerular microenvironment and as a cell delivery vehicle to replenish the podocyte population by cell transplantation. After creating a native glomerulus‐like condition, the expression of multiple genes encoding growth factors and basement membrane factors that are strongly associated with podocyte maturation and functionality was significantly enhanced. Our in vivo results demonstrated that intrarenal transplantation of podocytes in the form of hybrid 3D cell spheroids improved engraftment efficiency and replenished glomerular podocytes. Moreover, the proteinuria of the experimental mice with hypertensive nephropathy was effectively reduced. These data clearly demonstrated the potential of hybrid 3D cell spheroids for repairing injured kidneys.

中文翻译：

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将由足细胞、间充质干细胞和血管内皮细胞组成的混合3D球体注射到肾皮质中可改善肾功能并补充肾小球足细胞


足细胞是高度分化的上皮细胞，对于维持肾脏中的肾小球滤过屏障至关重要。足细胞损伤和耗竭是肾脏疾病病理进展的主要原因。尽管细胞疗法被认为是治疗肾损伤的肾移植的一种有前途的替代方法，但在改善肾功能方面所产生的治疗效果有限，可能是由于移植细胞的大量损失。在此，由足细胞、间充质干细胞和血管内皮细胞组成的混合三维（3D）细胞球体被设计来模拟肾小球微环境，并作为细胞递送载体通过细胞移植补充足细胞群。在创建天然肾小球样条件后，编码与足细胞成熟和功能密切相关的生长因子和基底膜因子的多个基因的表达显着增强。我们的体内结果表明，以混合 3D 细胞球体形式肾内移植足细胞可提高植入效率并补充肾小球足细胞。而且，高血压肾病实验小鼠的蛋白尿也得到有效降低。这些数据清楚地证明了混合 3D 细胞球体修复受损肾脏的潜力。