Treating Diabetes With Transplanted Cells

Treating Diabetes With Transplanted Cells

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Treating Diabetes with Transplanted Cells


Seventy-five years ago the type of diabetes that affected children and
young adults was lethal. In the 1990's investigators found that a hormone, that
was produced in Islets of Langerhans, was not being produced in diabetes
patients. This hormone, called insulin, enables other cells to take up sugar
glucose from the blood for energy. Diabetes patients who were not making insulin
had glucose from food accumulating in the blood while other tissues were
starving. Their are two types of diabetes. Type 1 diabetes has ceased completely
from making insulin and the people who had this kind usually died. Type 2
diabetes still makes a little insulin so suffers of this type usually lived.
In the 1920's prospects for people who suffered from type 1 diabetes
increased when it was learned that insulin extracted from animals and placed in
humans could prevent death. Unfortunately, this is not a cure. Patients can get
potentially fatal diabetes-related disorders. These include blindness and, or
kidney failure. Atherososclerosis, numbness and pain in extremities caused by
narrowed vessicles, may also be a problem. These effects are caused because
insulin injections can't perfectly mimic naturally made insulin.
That's why a therapy that maintains glucose values within normal from
the 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 insulin
production. Successful grafts would also prevent diabete-related ills.
At Paul E. Lacy's lab, experiments have been done for twenty- five years
on such a process. At first they were just trying to understand the mechanics of
hormone secretion. To start this they needed a way to separate islet clusters
from the pancreas. These constitute only 2% of the entire pancreas, though, and
are scattered throughout it. In 1967 they found a solution and took the islets
from rats. These islets were transplanted in inbred rats to see if it would
control insulin production in diabetes patients. It was a success and kept blood
sugar levels normal. It even fixed early complications in the eyes and the
kidneys.
The next step was to test the process on humans. Unfortunately, the
process that was used to separate rat islets from the pancreas did not work on
humans. They had to find a new way to solve the problem. The problem took a few
years to solve but in the mid 1980's they finally found a semi-automatic method
to do it. This method managed to isolate 400,000 islets from the pancreas. It
would take just the amount they estimated to maintain the blood sugar level.

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     In 1986 the first experiment started. A lot of immune-suppresent drugs
are needed so the foreign tissue would not be rejected. These drugs are risky,
though, so the experiment was performed on patients who have had kidney
transplants and are already on these drugs. They decided that the best place to
place the islets was into the portal vein leading to the pancreas. This would
give the islets nourishment from the beginning and would be less risky than
placing them directly into the pancreas.
The results were encouraging. Subjects were given 400,000 islets and the
grafts worked. But it was not enough to stop insulin injection. Later when the
islets 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 and
stored. Since 1990 about 145 patients have had the process done. Most were
unable to control the blood sugar level. Strain on the islets may have been a
problem and in some cases enough probably weren't used.
Doctors are proposing to give these transplants with graphs even though
the results weren't perfect. The process is less costly and easier than complete
pancreas transplantation.
     Many concepts have been considered though to solve the last part of the
problem. One is being looked into by Kevin J. Lafferty. That is, that if you
destroy passenger luekocytes, the tissue would not be rejected.This has been
attributed to the theory that it takes two signals for host white blood cells to
attack 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, that
kills the passenger luekocytes without hurting the hormone-producing cells. He
placed 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 treated
separately and so is not practical for humans who need much, much more islets. A
solution 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 tried
because of the theory that diabetes is caused by an autoimmune process that
differs from rejection. This process perceives beta cells, specific cells that
produce insulin, as foreign tissue and destroy them. Therefore even if a
transplant is fully successful the bets cells will be destroyed. To cure
diabetes, islets that do not match those of the recipients islets must be
injected. Another solution is also to enclose these islets in a semipermeable
plastic membrane. If pore size is ideal, membranes let glucose reach islets and
allow insulin to made while keeping the islet safe.
     William L. Chick developed a technique that puts islets in a plastic
tube that allows blood flow in where it contacts the islets. Then insulin passes
out. It worked for a while until the tube became clogged. The biocompatibility
has 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. This
could cause internal bleeding. The tubes could also clog arteries.
     Franklin Lim and Anthony M. Sun has also prepared islets by suspending
them in alginate and enclosing them. It has been placed in rats and worked but
the islets died from lack of nutrients caused by the alginate. Plastic-coated
droplets are more biocampatible and have temporarily reversed diabetes in
patients. These capsules are very small but are needed in such large amounts
that to be feasibly worked they would have to be even smaller. A way to remove
these capsules readily is also needed.
     Paul E. Lacy has also developed a way using islets covered in jelled
alginate and then enclosed in a hollow, semi spherical acrylic fiber that has
amazingly biocompatibility. This procedure maintained normal blood sugar level
in a rat for an entire year. It is being tested on humans.
     Research is also going on to make a fully artificial pancreas. This
device would be able to monitor blood sugar and release just the right amount of
insulin in response. A device that is at once small, durable and accurate is
still trying to be devised though.
     Before these a solution can be wide spread used though, enough donor
islets must be found beside cadavers due to the amount of people that suffer
from diabetes. Some other places islets might be found are in fetuses, many
scientists hope to find a way to implant insulin-making cells alone which can be
grown in labs, and pig islets are also a major possibility. Transplanting of
encapsuled cells may also help a lot of other people beside diabetes patients
including; Hemophiliacs and people suffering from Parkinsons disease.
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