Bioengineered rat kidneys developed by Massachusetts General Hospital (MGH)
investigators1 successfully produced urine both in a laboratory
apparatus2(装置) and after being transplanted into living animals. In their report, receiving advance online publication in Nature Medicine, the research team describes building
functional3 replacement4 kidneys on the structure of
donor5 organs from which living cells had been stripped, an approach
previously6 used to create bioartificial hearts, lungs and livers. "What is unique about this approach is that the native organ's architecture is preserved, so that the resulting
graft7 can be transplanted just like a donor kidney and connected to the recipient's
vascular8(血管的) and urinary systems," says Harald Ott, MD, PhD, of the MGH Center for Regenerative Medicine, senior author of the Nature Medicine article. "If this technology can be scaled to human-sized
grafts9, patients suffering from renal failure who are currently waiting for donor kidneys or who are not transplant candidates could theoretically receive new organs
derived10 from their own cells."
Around 18,000 kidney transplants are performed in the U.S. each year, but 100,000 Americans with end-stage kidney disease are still waiting for a donor organ. Even those fortunate enough to receive a transplant face a lifetime of immunosuppressive drugs, which pose many health risks and cannot totally eliminate the
incidence(发病率) of
eventual11 organ
rejection12.
The approach used in this study to engineer donor organs, based on a technology that Ott discovered as a research fellow at the University of Minnesota, involves stripping the living cells from a donor organ with a
detergent13 solution and then repopulating the collagen scaffold that
remains14 with the appropriate cell type -- in this instance human
endothelial(内皮的) cells to replace the
lining15 of the vascular system and kidney cells from newborn rats. The research team first decellularized rat kidneys to confirm that the organ's complex structures would be preserved. They also showed the technique worked on a larger scale by stripping cells from pig and human kidneys.
Making sure the appropriate cells were seeded into the correct portions of the collagen scaffold required delivering vascular cells through the renal
artery16 and kidney cells through the ureter.
Precisely17 adjusting the pressures of the solutions enabled the cells to be
dispersed18 throughout the whole organs, which were then cultured in a bioreactor for up to 12 days. The researchers first tested the repopulated organs in a device that passed blood through its vascular system and drained off any urine, which revealed evidence of limited filtering of blood,
molecular19 activity and urine production.