The effective bioengineering method of implantation decellularized renal extracellular matrix scaffolds

Abstract

End stage renal disease (ESRD) is a progressive loss of kidney function with a high rate of morbidity and mortality. Transplantable organs are hard to come by and hold a high risk of recipient immune rejection. We intended to establish a more effective and faster method to decellularize and recellularize the kidney scaffold for transplant and regeneration. We successfully produced renal scaffolds by decellularizing rat kidneys with 0.5% sodium dodecyl sulfate (SDS), while still preserving the extracellular matrix (ECM) 3D architecture, an intact vascular tree and biochemical components. We recellularized the kidney scaffolds with mouse embryonic stem (ES) cells that then populated and proliferated within the glomerular, vascular, and tubular structures. After in vivo implantation, these recellularized scaffolds were easily reperfused, tolerated blood pressure and produced urine with no blood leakage. Our methods can successfully decellularize and recellularize rat kidneys to produce functional renal ECM scaffolds. These scaffolds maintain their basic components, retain intact vasculature and show promise for kidney regeneration.

Repopulating Decellularized Kidney Scaffolds: An Avenue for Ex Vivo Organ Generation

“…Similar experiments were performed by Guan et al , in which rat scaffolds were seeded with murine embryonic cells via the renal artery and the ureter as well [ 33 ]. Orthotopic transplantation of reseeded scaffolds into rats allowed for initial blood flow and no observable signs of rejection were observed; however, by two weeks post implantation, the renal artery and vein had thrombi blocking sufficient blood flow [ 33 ].…”

“…Similar experiments were performed by Guan et al , in which rat scaffolds were seeded with murine embryonic cells via the renal artery and the ureter as well [ 33 ]. Orthotopic transplantation of reseeded scaffolds into rats allowed for initial blood flow and no observable signs of rejection were observed; however, by two weeks post implantation, the renal artery and vein had thrombi blocking sufficient blood flow [ 33 ]. This is likely due to an absence of the correct cell type in the vasculature, which was provided by the HUVECs in the study by Song et al , as well as the inclusion of growth factors by the latter group to aid in differentiation of the NKCs [ 32 ].…”

A critical review of current progress in 3D kidney biomanufacturing: advances, challenges, and recommendations

“…However, a lack of glomeruli maturity meant that the constructs were unable to restore kidney-specific parameters. Similarly, Guan et al demonstrated that despite the initial acceptance of reseeded kidney scaffolds, insufficient blood supply due to thrombosis in the renal artery and rein resulted in transplant failure [199]. This was thought to be due to incorrect cell differentiation of cells populating the vasculature.…”

Reconstruction of structure and function in tissue engineering of solid organs: Toward simulation of natural development based on decellularization

“…Finesilver, Kahana, and Mitrani () seeded hESCs onto microscaffolds derived from decellularized renal ECM and found that ESCs could survive in the glomerular and tubular structures and differentiate into renal progenitors. Mice ESCs were perfused into decellularized renal ECM through the renal artery and ureter, which successfully colonized in the glomerular, vascular, and tubular structures (Bonandrini et al, ; Guan et al, ). After in vivo implantation, these recellularized scaffolds were able to gain reperfusion, produce urine, and sustain blood pressure.…”