Implantable Bioengineered Rat Kidney Tested
Bioengineered rat kidneys have successfully produced urine both in a laboratory apparatus and after being transplanted into living animals. Massachusetts General Hospital (MGH) investigators described building functional replacement kidneys on the structure of donor organs from which living cells had been stripped.
(Decellularized rat kidney )
Shown after reseeding with endothelial cells, to repopulate
the organ's vascular system, and neonatal kidney cells.
"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, 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 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 detergent solution and then repopulating the collagen scaffold that remains with the appropriate cell type – in this instance human endothelial cells to replace the lining 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.
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. The overall function of the regenerated organs was significantly reduced compared with that of normal, healthy kidneys, something the researchers believe may be attributed to the immaturity of the neonatal cells used to repopulate the scaffolding.
"Further refinement of the cell types used for seeding and additional maturation in culture may allow us to achieve a more functional organ," says Ott. "Based on this inital proof of principle, we hope that bioengineered kidneys will someday be able to fully replace kidney function just as donor kidneys do. 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."
Philip K. Dick fans recall the artiforgs from his 1969 novel Ubik, as well as the earlier references like the artificially grown organs from Larry Niven's 1968 novel A Gift from Earth.
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