Researchers have been working for
years to develop an artificial pancreas in the lab to help the millions of
people with type 1 diabetes. But what if the answer is to “recycle” the more
than 300 human pancreata from organ donors that aren’t currently being used?
Online ahead of print in the Annals
of Surgery, regenerative medicine researchers at Wake Forest Baptist Medical Center’s Institute for
Regenerative Medicine and colleagues report on the potential to use human
pancreata as the “hardware” of a new-generation, bio-artificial pancreas. The
pancreas is a large gland near the stomach that secretes insulin to regulate
the metabolism of glucose and other nutrients.
Currently, about 25 percent of the
approximately 1,300 pancreata recovered for transplant cannot be used due to
defects and other reasons.
“We see these unused organs as
potential ‘hardware.” The ‘software’ would be the patient’s own cells, so that
there would be no issues with rejection,” said lead author Giuseppe Orlando,
M.D., Ph.D., a transplant surgeon and regenerative medicine
researcher. “We believe this research represents the first critical step toward
a fully human-derived artificial pancreas.”
Currently, most patients who have type
1 diabetes must take injections of insulin because their bodies do not produce insulin
to regulate blood sugar levels. Other options, such as a pancreas transplant or
transplant of insulin-producing islet cells are rarely offered due to the lack
of suitable pancreas donors and the toxic effects of anti-rejection drugs. In
the U.S., for every 10,000 patients with type 1 diabetes, only three will
receive a pancreas transplant or islet transplant in their lifetime, according
to the authors.
The goal of the research was to
test the suitability of pancreata from organ donors as a platform for building a
new bio-artificial pancreas. First, the discarded organs were washed in a mild
detergent to remove all cells, a process that is known as decellularization. A
similar procedure is being used by Wake Forest Baptist regenerative medicine
researchers in efforts to engineer human kidneys, livers and intestine.
The goal of both projects is to develop
a new, potentially inexhaustible source of organs that would not require
patients to take powerful anti-rejection drugs. The idea is based on evidence
that the decellularized organs contain proteins and other substances that play
a vital role in the survival, welfare and function of the organ’s cells.
For the study, 25 human pancreata were
processed to remove cells. The researchers found that the framework of blood
vessels remained intact after the washing process. In addition, the researchers
are the first to report that numerous growth factors were retained in the
structures. Some of these proteins are essential in blood vessel formation,
cell proliferation and glucose metabolism.
In theory, these organ structures
could be re-populated with a patient’s own cells. Insulin-producing cells could
be generated from the patient’s skin cells or could come from the patient’s
pancreas. Cells to line the organ’s blood vessels (endothelial cells) could
also come from the patient’s pancreas. To test the compatibility of the decellularized
structures and new cells, the researchers placed both insulin-producing and endothelial
cells on the decellularized structures. In both cases, the organs structures
were cell-friendly and allowed the cells to attach, function and maintain their
original cell type.
Next, to test the ability of the
structures to grow new blood vessels, small samples of the cell-coated
pancreata structures were implanted in chicken eggs. The structures integrated
well with the developing environment of the chicken egg and generated
capillaries. For the first time, the authors also
conducted immunological tests to understand whether the structures would be
rejected by the immune system. Surprisingly, they found that the structures
actually regulated the immune response, suggesting that the engineered
pancreata could be used as adjuvant immunosuppressants.
“The early results are encouraging
and pave the way for further investigations to understand the interactions
between the organ structures and cells and to identify the optimal cell type to
achieve complete regeneration of the endothelium and islets,” said Orlando.
addition to the current research, Orlando represents Wake Forest Baptist as the
only U.S.-based researcher on a $9 million project to develop a cell-therapy
product to treat diabetes. The four-year effort, BIOCAPAN, is funded by the
European Commission. Orlando’s role is to use regenerative medicine
technologies to distill non-cellular materials from discarded pancreata. The
research team hypothesizes that the material may support the function of
insulin-producing cells and can form the basis of a new insulin-free treatment
for diabetes. (This project has received funding from the European Union’s
Horizon2020 research and innovation programme under grant agreement No 646272).
research reported in the Annals of Surgery is supported by unrestricted funds
from Liberitutti Foundation.
of the study were: Andrea Peloso, M.D., Ph.D., Ravi Katari, B.S., Guoguang Niu,
PhD, John P. McQuilling, Ph.D., Sivanandane Sittadjody, Ph.D., Alan C. Farney,
M.D., Ph.D., Samy S. Iskandar, MBBCh. Ph.D., Jeffrey Rogers, M.D., Robert J.
Stratta, M.D., Emmanuel C. Opara, Ph.D., Cristina M Furdui, Ph.D., and Shay
Soker, Ph.D., Wake Forest Baptist; Luca Urbani, Ph.D., Panagiotis Maghsoudlou,
B.S., Mario Enrique Alvarez Fallas, B.S., and Paolo De Coppi, M.D., Ph.D.,
Great Ormond Street Hospital, London; Paolo Cravedi, M.D., Ph.D., and Carolina
Purroy, M.D., Ph.D., Icahn School of Medicine at Mount Sinai; and Valeria
Sordi, Ph.D., Lorenzo Piemonti, M.D., Ph.D., and Antonio Citro, Ph.D., IRCCS
San Raffaele Scientific Institute, Milan, Italy.