Regenerative Medicine and Bioartificial Kidneys Could Aid Shortage of Donor Kidneys

For Guiseppe Orlando, MD, and Shuvo Roy, PhD, 2012 was a year of milestones for their respective research programs that ultimately will help combat the critical shortage of donor organs for kidney transplantation. The year 2013 promises to bring their work to further fruition.

Orlando, a transplant surgeon and scientist, headed the Wake Forest Institute for Regenerative Medicine research team that succeeded in creating acellular renal extracellular matrix (ECM) scaffolds through decellularization–recellularization technology. The scaffolds were applied to whole porcine kidneys.

“These kidneys maintained their innate three-dimensional architecture as well as their vascular system and may represent the ideal platform for kidney engineering,” said Orlando, who reported the research in the journal Annals of Surgery.

His goal is a bioengineered kidney that could be manufactured from the patient’s own cells.

For Roy, a bioengineer in the University of California at San Francisco’s (UCSF) Department of Bioengineering and Therapeutic Sciences, the goal is not to generate new renal tissue but to design reliable implantable renal assist devices—bioartificial kidneys —for end stage renal disease (ESRD) patients.

Last year, the U.S. Food and Drug Administration (FDA) selected the UCSF bioartificial kidney for its Innovation Pathway 2.0, because of the device’s “transformative potential” in ESRD and “its potential to benefit from early interactions with the FDA in the approval process,” according to the university.

Roy and the project’s medical director, William H. Fissell, MD, associate professor of clinical medicine, Vanderbilt University Medical Center, have been working for about 10 years with a multidisciplinary team of 40 researchers in nine U.S. laboratories to develop the bioartificial kidney, aiming for clinical trials by 2017.

Could donated kidneys produce scaffolds for populating ESRD patients’ own cells?

Orlando, who was an invited lecturer in the “Bioengineering and Informatics: Curing Renal Disease with Cells and Devices” session at Kidney Week 2012, implanted the acellular scaffolds in pigs and one month later removed them.

Pathological examination showed that the renal ultrastructure had not changed, but a nonspecific inflammatory response, which is normally triggered following any surgical trauma, had occurred, Orlando said.

Orlando and his colleagues next will evaluate the scaffolds in pigs after the structures have been seeded with kidney-specific cells and possibly other cell types, such as those that pave the blood vessels of organs to allow implantation.

If the research succeeds, Orlando said he envisions using donated human kidneys to produce the acellular scaffolds, which would be repopulated with the ESRD patient’s own cells.

Bioartificial kidney

To design the bioartificial kidney, Roy and colleagues took advantage of technological advances in microelectromechanical systems and nanotechnology. These technologies enabled the researchers to miniaturize the large-size extracorporeal renal assist device developed at the University of Michigan through the use of high-efficiency ultrafiltration membranes that can be mass produced.

The ideal bioartificial kidney would perform the kidney’s filtration functions as well as maintain water and salt balance, produce vitamin D, and regulate blood pressure and pH.

“We try to mimic a number of those functions through a combination of mechanical components—silicon filters that we have developed—with cells that we’ve harvested from human kidneys,” Roy said.

The current prototype can provide stable differentiated functions of renal tubule cells harvested from human kidneys in an engineered construct, the cell bioreactor, Roy said.

The team continues to build and test increasingly complex prototypes with improved silicon membranes. They also are experimenting with a combined hemofilter and cell bioreactor and are packaging the device for preclinical testing.

Roy also spoke at Kidney Week 2012.

January 2013 (Vol. 5, Number 1)