Surface modification of decellularized kidney scaffold with chemokine and AKI-CKD cytokine juice to increase the recellularization efficiency of bio-engineered kidney

Abstract

Chronic kidney disease (CKD) is a prevalent global health issue, primarily caused by glomerular dysfunction, diabetes, endovascular disorders, hypertensive nephrosclerosis, and other vascular diseases. Despite the increase in available organ sources, significant challenges remain in securing organ compatibility, prompting extensive research into creating a bio-artificial kidney free from immune rejection. In this study, a bio-engineered kidney was established using a stem cell chemoattractant within a bioreactor system; rBMSCs were used to recellularize the decellularized kidney scaffold coated with SDF-1α/AKI-CKD cytokine juice under mimic-hypoxic conditions as these chemokines and cytokines are crucial for the cell migration. LC-MS/MS proteomic analysis of the scaffold suggested that it contains various important proteins related to angiogenesis, cell migration, differentiation, etc. The in-silico binding simulation and Immunohistochemical (IHC) staining were utilized to detect the coated chemokines and cytokines. Cells were administered through both ureter and arterial routes of the kidney scaffold to differentiate into epithelial and endothelial cells. After 14 days of the recellularization process utilizing a mimic-hypoxia-induced bioreactor, the SDF-1α/AKI-CKD CJ-coated kidney scaffold exhibited high levels of cell attachment, migration, and proliferation in both the cortex and medulla. Additionally, the coating of the cytokines remarkably enhanced the expression of specific renal cell markers within the complex microfilter-like tubular structures. This study underscores a recellularization strategy that addresses the challenges associated with constructing bio-artificial kidneys and contributes to the growing field of bio-artificial organ research.