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Tissue Engineering Kidney Structures

Kidney transplantation for the treatment of terminal-stage kidney diseases is a well-established procedure with an excellent clinical outcome; currently, kidney transplants make up 70% of all organ transplants. In 2003, more than 2,000 patients received a kidney transplant as their first therapy, and the number of patients needing a kidney transplant grows steadily. However, the shortage of kidney donors is an unsolved problem that creates a transplant crisis. According to data from United Network for Organ Sharing, kidney patients account for 65,000 of the approximately 90,000 patients on the waiting list for all organ transplantation. Besides transplants, other strategies, such as extracorporeal dialysis, are in clinical use. However, in current hemodialysis or hemofiltration, synthetic semipermeable membranes are utilized only to substitute for the small solute clearance functions of the renal glomerulus; this does not replace the transport, metabolic, and endocrinologic functions of the tubular cells. Although researchers tried to combine a synthetic hemofiltration device with renal tubule cells derived from porcine kidney to replace certain physiologic function of kidney in acutely uremic animals, extracorporeal perfusion still has significant limitations in terms of morbidity, mortality, and cost. Therefore, extracorporeal dialysis is a partial, temporary treatment, not a radical solution for this problem. Engineering of a living, functional human kidney can solve this problem permanently. However, this is no established technology to tissue-engineer functional human kidney yet.

To this end, we recently initiated Charleston Bioengineered Kidney Project. The goal of this translational multidisciplinary project is to bioengineer a living, functional human kidney suitable for clinical transplantation. There are five major components in mammal nephrons: the renal corpuscle consists of a thin capsule of epithelial tissue (Bowman's Capsule) surrounding a ball of capillaries (glomerulus), the proximal convoluted tubule, the Loop of Henle, the distal convoluted tubule, and the collecting ducts. We demonstrated that kidney epithelial cells can form a cyst-like structure and then fuse into a renal tubule-like structure with appropriate polarity]. Using phase inversion technology, we fabricated biodegradable, elastic, hollow-fiber membranes from biocompatible polyurethane and seeded the membranes with kidney epithelial cells. Using laser micro-fabrication, we then created holes of controlled size and demonstrated that epithelial cyst-like structure can fuse with the epithelialized hollow fiber through those laser-drilled holes. Thus, we can create a seamless epithelial transition from hybrid synthetic-epithelial tubes (macro-structure of bioengineered kidney) to regenerated renal tubules in the permissive hydrogel system (micro-structure of regenerated renal tissue). We demonstrated the feasibility of fabricating four out of five essential components of a kidney nephron using animal cells. The glomerulus is the only element in the renal corpuscle that remains to be developed.