Injection of hybrid 3D spheroids composed of podocytes, mesenchymal stem cells, and vascular endothelial cells into the renal cortex improves kidney function and replenishes glomerular podocytes

Bioengineering & Translational Medicine

Li‐Wen Hsu¹  Chih‐Kuang Yeh²  Meng‐Yu Tsai³  Yun‐Wei Lee³  Wen‐Yu Yang³  Yu‐Jie Lin³  Li‐Chi Chen³  Chieh‐Cheng Huang³  Hsiang‐Hao Hsu⁴  Ya‐Ting Jhuang⁴  Pei‐Yu Hung⁴  Yi‐Ching Ko⁴ 

[1] Bioresource Collection and Research Center Food Industry Research and Development Institute Hsinchu Taiwan;Department of Biomedical Engineering and Environmental Science National Tsing Hua University Hsinchu Taiwan;Institute of Biomedical Engineering National Tsing Hua University Hsinchu Taiwan;Kidney Research Center, Department of Nephrology Linkou Chang Gung Memorial Hospital Taoyuan Taiwan;

关键词: cell spheroids;    cell therapy;    glomerulus;    kidney injury;    podocyte;   

DOI  :  10.1002/btm2.10212

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown