04-17-2013, 01:15 AM
(This post was last modified: 04-17-2013, 02:20 AM by Administrator.)
The problems of donor-organ shortage are well known in modern medicine. In case of kidney failure alone, only 18 out of 100 people receive a donor organ, the rest remain of waiting lists until critical failure and ultimately, death. Those that do receive a donor kidney are forced to live on immunosuppressant medication for the rest of their lives, and face a multitude of complications, either from rejection, or other complications concerning their immunocompromised state.
Several projects have been on the way, some for more than a decade now, attempting to engineer kidneys eligible for transplants. This approach, would, theoretically, avoid any immune system complications, and solve the organ-shortage problem.
Researchers of the Massachusetts General Hospital have bioengineered rat kidneys that successfully produced urine both in a laboratory apparatus and after being transplanted into living animals, an achievement long sought after in organ engineering research. In their research report, published in Nature Medicine, the scientists describe building functional replacement kidneys on the structure of donor organs from which living cells had been stripped off, 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. 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.” - explains Harald Ott, M.D., Ph.D., of the MGH Center for Regenerative Medicine, senior author of the paper.
Dr. Ott discovered, as a research fellow at the University of Minnesota, a new technique to bioengineer organs, and that technique was utilized in this project. It involves stripping the living cells from a donor organ with a detergent solution without damaging the fiber architecture of the organ, and then repopulating the collagen scaffold that remains with the appropriate cell type, in this case endothelial cells and nephrocytes. In this case, human endothelial cells were used to replace the lining of the vascular system and kidney cells were taken from newborn rats. The research team first decellularized rat kidneys to confirm that the organ's complex structures would not be destroyed or altered. They also showed the technique worked on a larger scale by stripping cells from pig and human kidneys.
To make sure that appropriate cells are in their appropriate positions, the researchers had to administer the endothelial lining of the blood vessels through the vascular system of the organ, and the nephrocytes through the ureter. By precisely adjusting the pressures of the solutions the researchers enabled the cells to be dispersed throughout the whole organs, which were then cultured and grown 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, molecular activity, and urine production, proving the concept that this organs in fact, worked, though at limited capacity.
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 any complications such as bleeding or clot formation. The overall function and capacity 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, it nonetheless proves a principle.
“Further refinement of the cell types used for seeding and additional maturation in culture may allow us to achieve a more functional organ. 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. 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.” Stated Dr. Ott.
Results published online, pre-print version; Nature Medicine
Several projects have been on the way, some for more than a decade now, attempting to engineer kidneys eligible for transplants. This approach, would, theoretically, avoid any immune system complications, and solve the organ-shortage problem.
Researchers of the Massachusetts General Hospital have bioengineered rat kidneys that successfully produced urine both in a laboratory apparatus and after being transplanted into living animals, an achievement long sought after in organ engineering research. In their research report, published in Nature Medicine, the scientists describe building functional replacement kidneys on the structure of donor organs from which living cells had been stripped off, 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. 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.” - explains Harald Ott, M.D., Ph.D., of the MGH Center for Regenerative Medicine, senior author of the paper.
Dr. Ott discovered, as a research fellow at the University of Minnesota, a new technique to bioengineer organs, and that technique was utilized in this project. It involves stripping the living cells from a donor organ with a detergent solution without damaging the fiber architecture of the organ, and then repopulating the collagen scaffold that remains with the appropriate cell type, in this case endothelial cells and nephrocytes. In this case, human endothelial cells were used to replace the lining of the vascular system and kidney cells were taken from newborn rats. The research team first decellularized rat kidneys to confirm that the organ's complex structures would not be destroyed or altered. They also showed the technique worked on a larger scale by stripping cells from pig and human kidneys.
To make sure that appropriate cells are in their appropriate positions, the researchers had to administer the endothelial lining of the blood vessels through the vascular system of the organ, and the nephrocytes through the ureter. By precisely adjusting the pressures of the solutions the researchers enabled the cells to be dispersed throughout the whole organs, which were then cultured and grown 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, molecular activity, and urine production, proving the concept that this organs in fact, worked, though at limited capacity.
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 any complications such as bleeding or clot formation. The overall function and capacity 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, it nonetheless proves a principle.
“Further refinement of the cell types used for seeding and additional maturation in culture may allow us to achieve a more functional organ. 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. 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.” Stated Dr. Ott.
Results published online, pre-print version; Nature Medicine
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