Development of a Bioartificial Kidney

The ability to develop tissues and organs for eventual human transplantation through a regenerative medicine approach has the potential to address and possibly solve the worldwide shortage of organs for transplantation. Tissue engineered tracheas and bladders--grown in a laboratory-- have been successfully transplanted into human patients (1, 2). Conceptually, the future clinical application of regenerative medicine to solid organ transplantation will involve removing the antigenic parenchyma from either non-transplantable human organs or animal organs (pigs), leaving only the extracellular matrix (ECM) as a scaffold. Cultured in a bioreactor, this scaffold supports homing and growth of progenitor cells derived from the intended recipient using induced pluripotent stem (iPS) cell technology. Over 95,000 patients in the United States are waiting for a kidney for transplantation; however, just over 17,500 kidney alone or kidney/pancreas transplants were performed in 2011 (HRSA/OPTN). Renal transplantation is life-saving, leads to decreased cardiovascular disease and improved quality of life compared to patients remaining on dialysis. Despite the benefits of renal transplantation and the expansion of the donor pool to include extended criteria organs, kidneys from donors after cardiac death, and those from living donors, renal transplantation still cannot be extended to all patients in need. A tissue engineering and regenerative medicine approach may be a long-term solution to solve the organ shortage problem; however, the cellular make-up of the engineered graft remains a challenge. The kidney is a spatially complex organ due to the specialized nature of the cellular components of the nephron. The kidney contains more than 20 different cell types, and so it would be exceedingly difficult, perhaps impossible, to orchestrate a rational, temporal sequence of introducing each mature cell type into a decellularized kidney scaffold to create a tissue engineered organ. Our collaboration, between my laboratory and Dr. Angela Wandinger-Ness from the University of New Mexico, presents a unique approach to address this dilemma. Our strategy is to repopulate a bioscaffold with renal progenitor cells and to allow these cells to differentiate within the scaffold, dependent upon spatially-oriented cues within the ECM. The purpose of our collaboration, and proposal, is to use human renal progenitor cells to develop a tissue engineered kidney and then demonstrate function in rodent model with renal failure (Figure 1). My laboratory has experience repopulating the renal vasculature with iPS-derived endothelial cells. It would be optimal to use iPS derived renal cells to likewise repopulate the parenchyma, but to date iPS-derived renal progenitor cells have not been characterized. Dr. Angela Wandinger-Ness from the University of New Mexico and I have an ongoing collaboration to differentiate primary human renal progenitor cells from cadaveric donor kidneys within a rodent kidney decellularized matrix. Dr. Wandinger-Ness is one of the few researchers worldwide that can isolate human renal progenitor cells from cadaveric kidneys with high purity and quantity. The advantage of our collaboration is that we combine an expertise in renal development and progenitor cell isolation (Dr. Wandinger-Ness) with expertise in tissue engineering and organ decellularization (Dr. Wertheim). Together, we are one of the few, if not only, groups in the world that can develop tissue engineered kidneys from human renal progenitor cells. This is m