Treating Diabetes with Transplanted CellsSeventy-five years ago the type of diabetes that affected children andyoung adults was lethal. In the 1990’s investigators found that a hormone, thatwas produced in Islets of Langerhans, was not being produced in diabetespatients. This hormone, called insulin, enables other cells to take up sugarglucose from the blood for energy.
Diabetes patients who were not making insulinhad glucose from food accumulating in the blood while other tissues werestarving. Their are two types of diabetes. Type 1 diabetes has ceased completelyfrom making insulin and the people who had this kind usually died. Type 2diabetes still makes a little insulin so suffers of this type usually lived.In the 1920’s prospects for people who suffered from type 1 diabetesincreased when it was learned that insulin extracted from animals and placed inhumans could prevent death.
Unfortunately, this is not a cure. Patients can getpotentially fatal diabetes-related disorders. These include blindness and, orkidney failure.
Atherososclerosis, numbness and pain in extremities caused bynarrowed vessicles, may also be a problem. These effects are caused becauseinsulin injections can’t perfectly mimic naturally made insulin.That’s why a therapy that maintains glucose values within normal fromthe begging is needed. An ideal treatment would be the implantation of islets.This, in theory, would only have to be done once and would insure proper insulinproduction. Successful grafts would also prevent diabete-related ills.
At Paul E. Lacy’s lab, experiments have been done for twenty- five yearson such a process. At first they were just trying to understand the mechanics ofhormone secretion. To start this they needed a way to separate islet clustersfrom the pancreas. These constitute only 2% of the entire pancreas, though, andare scattered throughout it. In 1967 they found a solution and took the isletsfrom rats.
These islets were transplanted in inbred rats to see if it wouldcontrol insulin production in diabetes patients. It was a success and kept bloodsugar levels normal. It even fixed early complications in the eyes and thekidneys.
The next step was to test the process on humans. Unfortunately, theprocess that was used to separate rat islets from the pancreas did not work onhumans. They had to find a new way to solve the problem.
The problem took a fewyears to solve but in the mid 1980’s they finally found a semi-automatic methodto do it. This method managed to isolate 400,000 islets from the pancreas. Itwould take just the amount they estimated to maintain the blood sugar level.
In 1986 the first experiment started. A lot of immune-suppresent drugsare needed so the foreign tissue would not be rejected. These drugs are risky,though, so the experiment was performed on patients who have had kidneytransplants and are already on these drugs. They decided that the best place toplace the islets was into the portal vein leading to the pancreas. This wouldgive the islets nourishment from the beginning and would be less risky thanplacing them directly into the pancreas.
The results were encouraging. Subjects were given 400,000 islets and thegrafts worked. But it was not enough to stop insulin injection. Later when theislets were increased to 800,000, the insulin injections were able to be stopped,at least for a time. They also learned that the islets could be frozen andstored. Since 1990 about 145 patients have had the process done.
Most wereunable to control the blood sugar level. Strain on the islets may have been aproblem and in some cases enough probably weren’t used.Doctors are proposing to give these transplants with graphs even thoughthe results weren’t perfect. The process is less costly and easier than completepancreas transplantation.Many concepts have been considered though to solve the last part of theproblem. One is being looked into by Kevin J. Lafferty.
That is, that if youdestroy passenger luekocytes, the tissue would not be rejected.This has beenattributed to the theory that it takes two signals for host white blood cells toattack foreign agents. These two signals are sent by the passenger luekocytes.Unfortunately, to destroy these luekocytes you also destroy the hormone-producing cells.
Joseph M. Davie has devised a culturing technique, though, thatkills the passenger luekocytes without hurting the hormone-producing cells. Heplaced 1,500 treated islets from one rat strain to a portal vein of another.
There was no rejection! Unfortunately, the individual islets had to be treatedseparately and so is not practical for humans who need much, much more islets. Asolution was found in 1993. It is to take a few treated islets to a subject.This creates a tolerance for these islets which are transplanted untreated later.
This is still being experimented on, though.Another process is being experimented on also. This is being triedbecause of the theory that diabetes is caused by an autoimmune process thatdiffers from rejection.
This process perceives beta cells, specific cells thatproduce insulin, as foreign tissue and destroy them. Therefore even if atransplant is fully successful the bets cells will be destroyed. To curediabetes, islets that do not match those of the recipients islets must beinjected.
Another solution is also to enclose these islets in a semipermeableplastic membrane. If pore size is ideal, membranes let glucose reach islets andallow insulin to made while keeping the islet safe.William L. Chick developed a technique that puts islets in a plastictube that allows blood flow in where it contacts the islets. Then insulin passesout. It worked for a while until the tube became clogged.
The biocompatibilityhas been improved, though, and has worked for several months in a dog specimen.These tubes are thought to be able to rupture though in a rough situation. Thiscould cause internal bleeding. The tubes could also clog arteries.
Franklin Lim and Anthony M. Sun has also prepared islets by suspendingthem in alginate and enclosing them. It has been placed in rats and worked butthe islets died from lack of nutrients caused by the alginate. Plastic-coateddroplets are more biocampatible and have temporarily reversed diabetes inpatients.
These capsules are very small but are needed in such large amountsthat to be feasibly worked they would have to be even smaller. A way to removethese capsules readily is also needed.Paul E. Lacy has also developed a way using islets covered in jelledalginate and then enclosed in a hollow, semi spherical acrylic fiber that hasamazingly biocompatibility. This procedure maintained normal blood sugar levelin a rat for an entire year.
It is being tested on humans.Research is also going on to make a fully artificial pancreas. Thisdevice would be able to monitor blood sugar and release just the right amount ofinsulin in response.
A device that is at once small, durable and accurate isstill trying to be devised though.Before these a solution can be wide spread used though, enough donorislets must be found beside cadavers due to the amount of people that sufferfrom diabetes. Some other places islets might be found are in fetuses, manyscientists hope to find a way to implant insulin-making cells alone which can begrown in labs, and pig islets are also a major possibility. Transplanting ofencapsuled cells may also help a lot of other people beside diabetes patientsincluding; Hemophiliacs and people suffering from Parkinsons disease.