Functional Kidney Bioengineering with Pluripotent Stem-Cell-Derived Renal Progenitor Cells and Decellularized Kidney Scaffolds.
Recent advances in developmental biology and stem cell technology have led to the engineering of functional organs in a dish. However, the limited size of these organoids and absence of a large circulatory system poses limits to its clinical translation. To overcome these issues, decellularized whole kidney scaffolds with native microstructure and extracellular matrix (ECM) are employed for kidney bioengineering, using human-induced pluripotent-stem-cell-derived renal progenitor cells and endothelial cells. To demonstrate ECM-guided cellular assembly, the present work is focused on generating the functional unit of the kidney, the glomerulus. In the repopulated organ, the presence of endothelial cells broadly upregulates the expression level of genes related to renal development. When the cellularized native scaffolds are implanted in SCID mice, glomeruli assembly can be achieved by co-culture of the renal progenitors and endothelial cells. These individual glomerular units are shown to be functional in the context of the whole organ using a simulated bio-reactor set-up with urea and creatinine excretion and albumin reabsorption. Our results indicate that the repopulation of decellularized native kidney using clinically relevant, expandable patient-specific renal progenitors and endothelial cells may be a viable approach for the generation of a functional whole kidney.
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore.
Chan
C
Du
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore.
Karthikeyan
K
Narayanan
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore.
Meng Fatt
MF
Leong
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore.
Mohammed Shahrudin
MS
Ibrahim
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore.
Ying Ping
YP
Chua
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore.
Vanessa Mei Hui
VM
Khoo
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore.
Andrew C A
AC
Wan
D000818:Animals; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
cellular self-assembly; decellularized ECM scaffold; endothelial cells; kidney tissue engineering; renal progenitors