For people with type 1 diabetes, islet transplantation
offers the opportunity to live free of daily insulin injections. Islets, or the pancreatic cells that make insulin, are destroyed by the disease but can be replenished by a donor.
However, many challenges remain with this type of therapy. For example, approximately half of donor islets fail to thrive after many transplantations. Transplantation in the liver does not require surgery and islets have been clinically proven to function effectively there, but the liver does not provide a microenvironment suitable for islet survival. Clinicians and researchers have been searching for better transplant sites, said Hirotake Komatsu, M.D., Ph.D., a staff scientist at City of Hope, but it’s been a challenge to find a superior option — until now.
“We have shown that the efficiency in transplanting the cells just under the skin is comparable to that in the liver site, with the help of oxygen inhalation therapy,” said Komatsu, who works in the Department of Translational Research and Cellular Therapeutics
. “The time may come when patients can undergo an outpatient transplant surgery to place pancreatic cells under the skin, and bring a small oxygen tank and mask home with them to recover.”
In two recent papers, Komatsu and colleagues reported efforts to establish increased efficacy for pancreatic islet transplants under the skin by exploiting the benefits of oxygen therapy. This type of transplant would be less invasive and technically easy compared to the current transplant site of the liver. The technique effectively addresses two problems — the need for a better transplant site and islet cell death after transplantation.
In an August paper in the journal PLOS ONE
, Komatsu and others showed that lack of sufficient oxygen played a significant role in islet cell death and could potentially be remediated by simply supplying more oxygen to keep the islets viable.
“The idea is pretty simple,” said Komatsu. “If you have insufficient oxygen at a transplant site, then the solution is oxygen inhalation therapy.”
In a more recent paper, published online in October in American Journal of Transplantation
, he and the other researchers applied their theory, providing supplemental oxygen to animal models to increase oxygen levels at the skin transplant site.
“One paper gave the scientific clue for another,” said Komatsu. “First, we showed how depleted oxygen affects the pancreatic islet, then we applied oxygen to fulfill the depletion. The nice thing is that oxygen inhalation is simple and easily achievable.”
Nonetheless, Komatsu is working on ways to supply oxygen to the transplant site other than oxygen inhalation. He is collaborating on biomedical implant projects with Yu-Chong Tai, Ph.D., the Anna L. Rosen Professor of Electrical Engineering and Mechanical Engineering, Andrew and Peggy Cherng Medical Engineering Leadership Chair and head of the Micro-ElectroMechanical Systems laboratory at Caltech, which is dedicated to developing medical devices.
“Cutting-edge technology is compatible with this relatively simple idea for biomedical use,” said Komatsu. “Using state-of-the-art systems, we are aiming for translational applications for supplying oxygen after islet transplantation under the skin. Novel treatments may exist just down the road.”