Bioengineered rat kidney, cultured in a bioreactor
Bioengineered rat kidneys developed by MGH investigators successfully produced urine both in a laboratory apparatus and after being transplanted into living animals. In their Nature Medicine report, published online on April 14, the research team described building functional replacement kidneys on the structure of donor organs from which living cells had been stripped, an approach previously 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 graft can be transplanted just like a donor kidney and connected to the recipient’s vascular and urinary systems,” says Harald Ott, MD, PhD, of the MGH Center for Regenerative Medicine, and senior author of the Nature Medicine article. “If this technology can be scaled to human-sized grafts, patients suffering from renal failure who are currently
waiting for donor kidneys or who are not transplant candidates could theoretically receive new organs derived from their own cells.”
The study used a technology Ott developed as a research fellow at the University of Minnesota that involves stripping the living cells from a donor organ with a detergent solution and then repopulating the collagen scaffold
that remains with the appropriate cell type – in this instance human cells to replace the lining of the vascular system and kidney cells from newborn rats. The research team first stripped cells from rat kidneys to confirm that the organ’s complex structures would be preserved and then showed the technique worked on a larger scale by stripping cells from pig and human kidneys.
The researchers introduced the appropriate replacement cells into the collagen scaffold through the renal artery or the ureter and then cultured the organs in a bioreactor for up to 12 days. Bioengineered kidneys transplanted into living rats from which one kidney had been removed began producing urine as soon as the blood supply was restored, with no evidence of bleeding or clot formation. While the overall function of the regenerated organs was significantly less then that of normal, healthy kidneys, the researchers believe that may be caused by the immaturity of the neonatal cells used to repopulate the scaffolding.
“Based on this initial proof of principle, we hope that bioengineered kidneys will someday be able to fully
replace kidney function just as donor kidneys do,” says Ott. “In an ideal world, such grafts could be produced ‘on demand’ from a patient’s own cells, helping us overcome both the organ shortage and the need for chronic immunosuppression. We’re now investigating methods of deriving the necessary cell types from patient-derived cells and refining the cell-seeding and organ culture methods to handle human-sized organs.”
Read more articles from the 04/26/13 Hotline issue.