As scientists race to come up with ways to improve the human body through bio-artificial organs, one of the first such advances is likely to be the pancreas, which is being developed by Hebrew University team together with a Ramat Gan start-up.
Diabetes, a disease in which the body is unable to regulate its blood sugar levels, is growing to epidemic proportions. By 2035, nearly 600 million people will have some form of diabetes, either Type 1 formerly known as juvenile diabetes, in which people born with the condition cannot produce the insulin needed to regulate blood glucose, or Type II acquired diabetes, which usually develops in patients with weight problems.
“Our bioartificial pancreas is aimed at the most extreme cases of diabetes,” Prof. Eduardo Mitrani, who led the Hebrew Univeristy team, told The Times of Israel. “The engineered bio-pancreas can be implanted virtually anywhere in the body. There it can secrete the insulin the body needs in a regulated manner and deliver it directly to the bloodstream, thus eliminating the need for glucose measurement and attempts to regulate its levels by insulin injections.”
Diabetics, and the people they live and work with, are all too familiar with the routine. The patient must, at various times of the day, whip out a glucometer to figure out how much glucose is in the bloodstream. Then, it’s time to inject life-sustaining insulin, the hormone that enables the body’s cells to absorb and use glucose, which is needed to produce energy.
But it is extremely difficult to obtain a good steady control of glucose levels, said Mitrani. “That really illustrates the problem. Although there are guidelines and plenty of data, advanced diabetic patients still have a hard time figuring out exactly how much insulin to administer. In addition, insulin levels fluctuate throughout the day, so insulin needs can change by the moment. The main problem with diabetes is not the disease itself but the side effects caused by the fluctuations in glucose levels.”
Some researchers have attempted to overcome these problems by transplanting the body’s own pancreatic beta-cells in the hope that they will be able to jump-start the organ in patients with extreme cases of diabetes. “The problem with this approach today is that the vast majority of these transplanted cells die within two days of transplantation, so 50% of the patients are still insulin-dependent one year after transplantation. Five years later, only 10% remain insulin-independent,” said Mitrani.
Mitrani and Betalin Therapeutics, a Ramat Gan biotech start-up, are trying another approach, one they believe will be much more effective. Betalin’s Engineered Micro Pancreas (EMP) is based on the premise that in order for beta cells to properly function, it is necessary to provide an appropriate connective tissue scaffold that ensures the long term survival and proper function of the cells.
The proprietary platform technology developed by Mitrani has been licensed from the Hebrew University to Betalin via Yissum, The Hebrew University’s Technology Transfer Company.
Studies of the Betalin solution (published last month in the journal Tissue Engineering Part A) show that human islets, or beta cells derived from them in EMPs, function in vitro similarly to freshly dissected pancreatic islets – meaning that they produce insulin immediately, and continue to do so. The tests showed similar, regulated insulin levels for over three months, as compared to the manual insertion method, where the cell islets retained functionality for only a few days.
In addition to supporting regulated levels of insulin secretion, the EMPs quickly integrate into the body and “connect to the network” by inducing the formation of a proper vascular network that connect to the nearest blood vessels, said Mitrani.
“The micro pancreas aims at solving problems currently associated with transplantation of naked islets. In our system, prior to transplantation, islets are cultured within a biological scaffold that supports their survival, leading to long term functionality of the majority of the cells.”
The technology is being tested in several beta studies in Israel and the company is raising money for further tests and approval by the FDA and its Canadian counterpart Health Canada in order to start clinical trials in US and Canada. If all goes well, an artificial pancreas could be on the market within five years.
Mitrani collaborated with Prof. James Shapiro, Medicine and Surgical Oncology, University of Alberta, Canada on the project.
“We have been collaborating for the past two years with Prof. Mitrani to explore his most promising approach for providing a stable extracellular matrix combined with our highly successful ‘Edmonton Protocol’ islet cell transplant treatment in Type 1 diabetes. If Betalin’s new microscaffold technique continues to demonstrate efficacy, it has the potential to substantially improve cellular engraftment and survival both for islets and potentially for stem cell engraftment in future for clinical application,” Shapiro said.