Progress towards developing replacement kidneys in vitro
Researchers at Wake Forest Baptist Medical Center (NC, USA) have reported the progress in their quest to build replacement kidneys in the lab.
The team's goal is to make use of the more than 2,600 kidneys that are donated each year, but must be discarded due to abnormalities and other factors. The aim is to “recycle” these organs to engineer tailor-made replacement kidneys for patients. The study was recently published in Transplantation.
“We believe the two studies we are reporting provide critical information to the booming field of organ bioengineering as it applies to the kidney,” commented Giuseppe Orlando who is part of the Wake Forest Institute for Regenerative Medicine team aiming to recycle human kidneys.
The process begins by removing all cells from the discarded organ. The idea is to replace these cells with a patient’s own kidney stem cells, making a tailor-made organ and avoiding the risks of rejection as well as the use of anti-rejection medication.
To assess whether the decellularized organs would be a suitable for engineering, the researchers evaluated whether decellularization affects the glomerulus, a small sac of capillaries which are vital for filtering contaminants out of the body. The team also screened the kidney structures to see if they retained growth factors, known to play an important role in the kidney’s function.
The findings were positive and demonstrated that the size, structure and function of the micro-vessels in the glomerulus as well as growth factors were preserved after the decellularization process.
“These growth factors play a vital role in the formation of new vessels and kidney cells,” explained Orlando. “The fact that they are preserved means they can potentially facilitate the repopulation of cells into the structure and reduce the potential of clot formation.”
In a separate study, published in CellR4, the team reported on the interactions that occur when stem cells are placed on the decellularized kidneys.
“Understanding the interaction between the kidney structure and cells, as well as the choice of cell type to use, is an important challenge to address before a viable and functioning kidney structure can be manufactured and transplanted into patients,” explained Orlando.
The team seeded stem cells derived from amniotic fluid onto sections of the kidney structures. In this first study to describe the long-term results of this process, the results indicated that the stem cells were able to proliferate when placed on the structures and were functionally active as demonstrated by the secretion of growth factors.
“These results indicate that discarded human kidneys are a suitable platform for engineering replacement kidneys and that when cells are added, the structures behave as an effective and viable biosystem,” concluded Orlando.
The researchers are now looking into identifying the appropriate cells to regenerate both the vascular compartment of the kidney as well as the compartment of the kidney responsible for blood filtration.
Peloso A, Petrosyan A, Da Sacco S et al. Renal Extracellular Matrix Scaffolds From Discarded Kidneys Maintain Glomerular Morphometry and Vascular Resilience and Retains Critical Growth Factors.Transplantation, doi: 10.1097/TP.0000000000000811 (2015) [Epub ahead of print];
Wake Forest Baptist Medical Center press release: http://www.wakehealth.edu/News-Releases/2015/New_Discoveries_Advance_Efforts_to__Build_Replacement_Kidneys_in_the_Lab.htm