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May 29th, 2012
Date: May 19, 2012 8:46:08 PDT
To: Scott King <email@example.com>
Subject: A couple a questions from an interested type 1 diabetic.Greetings Mr. King,Let me first say that I am very impressed and intrigued by the work your group is doing with islet cell encapsulation techniques, very interesting stuff. My name is Curtis and I’ve been suffering from type 1 diabetes for just about 5 years now (diagnosed at 19). I have a couple of questions about the large scale animal model trials that are being/have been undertaken with islet cell encapsulation and transplant; if you have the time to answer them I’d greatly appreciate it.Firstly, one of the major hurdles in utilizing islet cell encapsulation as a cure for diabetes is the availability of islet cell donors; I was wondering if xenografts are a possibility in this regard. If the alginate that is used to encapsulate the islet cells is truly “immunoinvisible,” should islet cells from animal donors not function perfectly well? Also, I was wondering where exactly these encapsulated islet cells are being transplanted; I’ve read in some article that one of the main problems with encapsulation techniques is the adequate flow of oxygen and other nutrients, is this also the case with encapsulated islet cell transplants?As a undergraduate medical student involved in cancer research at the moment, I can appreciate the amount of work you have put into this project to get it to where it is today. I sincerely thank you for your efforts and hope your upcoming clinical trials are fruitful! Regards,Curtis I.
I am always happy to hear from someone who is studying for medical research and at the same time copes with type 1 diabetes. Keep up the good work. I hope you can contribute to our understanding of cancer, and I hope your contribution will be clinically useful.
To your questions.
Xenografts are the most promising mid-term source of islets to treat diabetics. The long-term source which would make islets available in great abundance would be stem cells that have been transformed into functional islets. Researchers in this area have achieved milestones. I project that seven to twenty years of research are required to achieve stem cell islets that are safe and effective. The immediate source of islets is human cadavers, the source for the vast majority of islets implanted to date.
It is generally thought that the pig is the most promising source of xenograft islets. Living Cell Technology of Auckland, NZ, is doing clinical studies with microencapsulated pig islets. Pig insulin is very similar to human insulin, and the insulin release kinetics of human and porcine islets are similar.
Our colleague Jonathan Lakey is developing a new method for isolating pig islets at the University of California – Irvine. His method promises high purity with greatly reduced cost. Right now we are designing studies that will implant Islet Sheets incorporating his porcine islets. The first recipient will be a pig. If the diabetic pig model behaves well (and we believe it will), in the future we will try other species’ islets in the pig model.
It has long been believed that alginate capsules do not protect xenografts to prevent rejection. The concept was the the tissue sheds antigen, and the xeno antigens stimulate immune responses. However, a growing literature suggests that advances in alginate and encapsulation methods are reducing reactions to encapsulated xenografts. Our own research shows the same trend. Randy Dorian, our theorist and seer, believes that ultimately xenografts and allografts will behave the same. Thus xenografts show clinical promise.
Several sites are useful in Islet Sheet implantation. Essentially any flat site with limited mobility seems compatible with the sheet. (An intestinal mesentery is a counter-example; it is too flexible.) We have our eye on two sites. The first is the peritoneal cavity. This is promising because most of the insulin would drain into the portal vein and reach the liver in a physiological way. The second is the subcutaneous space. The advantages here are surgical ease and its reputation of being an oxygen-rich site. We will be comparing these sites in both pigs and dogs.
Speaking of reputation, the peritoneal cavity is reputed to have only modest levels of oxygen. In fact, we have searched the scientific literature for proven measurement of this but failed to find such proof.
In any case, you are quite right that the availability of oxygen is an important factor limiting the function of islets in the Islet Sheet. We are exploring multiple methods for increasing oxygen supply. One that has proven successful is putting islets near the surface of the sheet so that oxygen diffusion need occur over only a short distance. We have some high-tech concepts in development too.
Thanks for your queries. If you have any others, please write again.