But what of the hundreds of thousands of patients with chronically diseased organs? Bioartificial-organ technology could restore their health as well-if it can make the leap from today’s temporary, external devices to long-term implants. Success with extracorporeal devices is inevitably stirring hope for bioartificial implants to treat this much larger need. Though researchers have pursued the idea since at least the 1970s, the field had been all but abandoned after continual disappointment. The problem: researchers couldn’t find a way to fully shield the cells inside an implanted device from recipients’ immune systems. Studies of encapsulated liver, pancreatic, and kidney cells have all run into problems due to immune rejection.
In fact, the porous plastic fibers that protect the cells in current bioartificial kidneys and livers from assault have failed in implants time and again. Their minute openings can defend against immune cells, but smaller armaments of the immune system, such as antibodies, can still penetrate the implant and, over time, break down its cells. It’s not a problem in temporary external devices, but in an implant, the detritus from dying cells passes out to the surrounding tissues, prompting scarring and blood clots. Eventually this seals off the implant, starving the cells still living inside.
Advances in nanotechnology could provide the solution: a material able to handle the seemingly contradictory tasks of isolating the cells from the immune system while allowing them to actively participate in the body’s function. Boston University biomedical engineer Tejal Desai believes nanotech can help fashion capsules with pores that can protect implants from even the tiniest immune invaders. “We can achieve absolute control over what gets into the system, what gets out,” says Desai.
Desai is developing a bioartificial pancreas that could extend diabetics’ lives and free them from pinpricks. She starts with silicon and etches it full of holes with techniques adapted from microchip production. The holes are 12 to 18 nanometers across, a fraction smaller than an antibody molecule. Desai then shapes the porous silicon into a small capsule or disc and fills it with living, human pancreatic cells. Surgically implanted in rats whose pancreases have been destroyed, these silicon capsules have elicited none of the clotting or scarring that doomed earlier implants. Moreover, insulin produced by the implanted cells maintained the rats’ blood sugar levels through the two-week test period, sustaining rats that would otherwise have perished in a matter of days. Within a year, Desai hopes to begin tests in large animals (probably dogs) of a prototype implant for diabetics.
William Fissell, a researcher in Humes’s University of Michigan lab, believes that similar silicon membranes could be the key to bioartificial kidney implants. But unlike Desai’s pancreatic implants, a bioartificial kidney must filter more than 100 liters of fluid each day. That’s easy for a large external cartridge with pumps to do, but filtering that much fluid is difficult in a much smaller implant, especially when nanopores constrain the exchange of fluid. The challenge is to design a material whose openings pass liquid efficiently and can support many tubule cells, yet which still protects the cells from antibodies. Fissell is already testing an elegant solution: stretching nanopores into elongated nanoslits with far more efficient fluid dynamics. If these slits can keep the antibodies out and filter fluids using only the body’s blood pressure, bioartificial kidney implants might one day replace dialysis for patients with chronic kidney failure.
But until then, external devices like the kidney-in-a-cartridge are the best hope. Emil Paganini, a leading dialysis authority at the Cleveland Clinic, is convinced of the bioartificial kidney’s potential, and the technology has not disappointed him. Five of Paganini’s patients were among the first 10 treated. He vigilantly followed their 24-hour treatment and witnessed consistent improvement. In one case, a patient’s response to the treatment astounded even this seasoned physician, who has seen his share of against-the-odds recoveries: the young man’s kidneys, poisoned by antifreeze, began to function again while his blood flowed through the bioartificial kidney, then shut off when the device was removed. “That blew my mind,” says Paganini. The patient’s kidneys eventually rebounded, and today the man is healthy.
After decades of frustrating research on purely artificial organs, such experiences are redefining the possibilities of organ replacement, reviving hopes for the struggling field. As Paganini puts it, “The concept of a bioartificial organ is in and of itself exciting.” But what’s even more exciting to physicians like him is that bioartificial organs, hybrids of the living and the synthetic, could soon be saving thousands of lives.