Researchers at Wake Forest Baptist Medical Center report progress in their quest to
build replacement kidneys in the lab. The teams’ 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 scientists aim to “recycle” these organs to engineer tailor-made
replacement kidneys for patients.
“We believe the two studies we are
reporting provide critical information to the booming field of organ
bioengineering as it applies to the kidney,” said Giuseppe Orlando, M.D., Ph.D.,
a transplant surgeon and regenerative
medicine researcher. Orlando is part of a team at the Wake Forest Institute
for Regenerative Medicine aiming to recycle human kidneys. Another group at the
institute is doing the same thing with pig kidneys.
The process begins by washing the discarded
organs in a mild detergent to remove all cells. The idea is to replace these
cells with a patient’s own kidney stem cells, making a tailor-made organ that
would not be rejected and wouldn’t require the use of powerful anti-rejection
medication. But are the organs a suitable platform for engineering after going
through the process to remove cells?
To help answer that question, the
researchers evaluated whether the washing process affects a small sac of
capillaries in kidneys called the glomerulus. These vessels, which are vital to
the kidney’s role of filtering contaminants out of the body, operate at a
pressure that is at least three times higher than other capillaries in the
body. The scientists injected resin into the structures to measure vessel size
and used pulse-wave technology to measure pressure within the vessels. The
researchers also screened the kidney structures to see if they retained growth
factors that play an important role in function.
In the journal Transplantation,
the research team reports that the size, structure and function of the
micro-vessels in the glomerulus are preserved after the cell-removal process. In
addition, vital proteins known as growth factors that regulate cell growth and
function are retained within the kidney structures.
“These growth factors play a vital
role in the formation of new vessels and kidney cells,” said 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 the
journal CellR4, the team reported on the interactions that occur when stem
cells are placed on kidney structures that have been through the cell removal
“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,” said
The team seeded stem cells derived
from amniotic fluid onto sections of kidney structures. In this first study to describe
the long-term results of this process, the scientists observed that the stem
cells proliferated when placed on the structures and were functionally active
as demonstrated by the fact that they secreted chemicals and growth factors
involved in such critical pathways as inflammation and the formation of new
“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,” said Orlando.
The researchers’ next steps are to
identify the appropriate cells to regenerate the vascular compartment of the
kidney as well as the compartment of the kidney responsible for blood
The research reported in Transplantation
was funded by the Liberitutti Foundation.
on the Transplantation paper were Andrea Peloso, M.D., Ph.D., Christopher
Booth, B.S., Jao Paulo Zambon, M.D., Ph.D., Shay Soker, Ph.D., and Robert J.
Stratta, M.D., Wake Forest Baptist Medical Center; John Robertson, VMD, Ph.D.,
Timothy O’Brien, BSME, and Charles Aardema, B.S., VA Tech; and Stgik Petrosyan,
B.S., Stefano Da Sacco, Ph.D., Robert De Filippo, M.D., and Laura Perin, Ph.D.,
University of Southern California.
on the CellR4paper were Andrea Peloso, M.D., Ph.D., Zang Wang, Ph.D., Ravi
Katari, B.S., Alan C. Farney, M.D., Ph.D., Jeffrey Rogers, M.D., Robert J.
Stratta, M.D., and Shay Soker, Ph.D., Wake Forest Baptist; and Stefano Da
Sacco, Ph.D., S. Sedakyan, Ph.D., Roger E. De Filippo, M.D., Laura Perin,
Ph.D., and Astgik Petrosyan, B.S., University of Southern California.