Regeneration and experimental orthotopic transplantation of a bioengineered kidney

Abstract

Over 100,000 individuals in the United States currently await kidney transplantation, while 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney’s architecture and function, and permit perfusion, filtration, secretion, absorption, and drainage of urine. We decellularized rat, porcine, and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells, then perfused these cell-seeded constructs in a whole organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused via their intrinsic vascular bed. When transplanted in orthotopic position in rat, the grafts were perfused by the recipient’s circulation, and produced urine via the ureteral conduit in vivo.

Dual-Purpose Bioreactors to Monitor Noninvasive Physical and Biochemical Markers of Kidney and Liver Scaffold Recellularization

“…Decellularization of livers and kidneys through perfusion of detergent solutions through the vasculature has been well documented 3,4 -with technical feasibility demonstrated using both large animal and humanscale organs [5][6][7][8] as well as small animal organs for repopulation with stem or immature progenitor cells. 7,[9][10][11][12][13] The current challenges and limitations to organ and tissue engineering have shifted to the cellular repopulation phase of tissue development where donor cells are reintroduced into wholeorgan ECM scaffolds; however, very little detail is typically provided describing bioreactor construction despite the identification of specific design features that are critical to optimize scaffold recellularization and overall function. 14 Herein, we discuss the evolution of two bioreactors for liver and kidney scaffold recellularization and address specific design considerations that not only allow these devices to achieve optimal cell delivery to each scaffold but also allow for noninvasive monitoring of cell growth.…”

The bridge between transplantation and regenerative medicine: Beginning a new Banff classification of tissue engineering pathology

“…A, Pencil sketch by Korey Fung based on Song et al24 image showing misshapen tubule with multiple lumens and missing cells in the glomerulus and interstitium. B, Pencil sketch by Korey Fung based on image from Song et al24 showing podocin‐positive podocytes wandering in the interstitium…”

“…B, Pencil sketch by Korey Fung based on image from Song et al24 showing podocin‐positive podocytes wandering in the interstitium…”

“…It would be ideal if the tissue engineering pathology classification we create is not something isolated on its own, idiosyncratic, and based mainly on abnormalities seen in rodent models,24, 25, 27 but fits within a larger human context. A partnership with the newly described human cell atlas project of Aviv Regev and Sarah Teichmann would be highly desirable (see Supplemental Material)32 as would a partnership with “liquid biopsy” systems for detecting circulating DNA in cancer diagnosis 33…”

A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord

“…Tissue engineering–based regenerative medicine has now entered a new era of applying implantable prebuilt tissue or organoid to repair tissue loss 17. Buoyed by the success in constructing functional neural networks from adult stem cells in vitro to repair SCI in our previous studies,11, 18 the present study has constructed a SCLT simulating the major cellular composition of the gray matter as well as the white matter of the spinal cord.…”