Mark. . .what can you tell me about TP/ICT

[Guest guest]

Hi . My name is I had the TP/ICT also by Dr. Sutherland. If you

have any questions for me, maybe I can help you too. Sincerely

VanderPan

[Guest guest]

Mark,

What and all information can you give me about TP/ICT? I want to know

everything and anything. How long the surgery takes, etc., etc.

Thanks.

T. (Ohio).

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[Guest guest]

Historically, the early complications with the exocrine portion of

the graft(98% of the pancreas is exocrine tissue), led to the idea of

isolating and transplanting the islets in a more easy and non-

surgical way. It continues to be deemed a promising approach.

Pancreases for islet isolation are usually procured from cadaver

donors. With a current islet transplant success rate of only 10%,

putting a living donor under surgical risk for islets would generally

not be justified (unlike a pancreas transplant). After the Islets of

Langerhans, which contain the B-(insulin producing) cells, are

separated from the exocrine tissue (islet isolation) by a machine,

they may be cultured for 2-3 days before transplantation. Under X-ray

guidance islets are injected into the recipient's portal vein. Once

in the portal vein, the blood flow and pressure carries the islets to

the liver where they encounter small diameter capillaries that cannot

be traversed by the islets. In such a mechanical way the islets stay

in place, and new capillaries incorporate them in an anatomical form.

An islet transplant alone from another person (allograft) is still on

its way to be perfected . Islets present a special and not fully

understood susceptibility to rejection and to side effects of the

immunosuppressants that prevent the cells from functioning or

surviving. Furthermore, there is not yet a marker to indicate

rejection episodes and thus the opportunity to reverse the

immunological attack is missed.

At the present islet-kidney transplantation is performed for

individuals that need a kidney but cannot have extensive surgery.

Although the insulin independence percentage is lower than for

pancreas transplant, 1/3 of the recipients have improved glucose

control. Islet transplant alone, though, for people whose pancreas is

removed to alleviate pain from pancreatitis , can be done with a 75%

success. In these cases the recipient's own pancreas is the source of

the islets (islet autograft, Iaut.) with no need for

immunosuppression. This fact and the appearance of new drugs (now

under experimentation) encourage patients, physicians, insurance

companies and pharmaceuticals to keep trying.

{top]

E.R. Sutherland, M.D., Ph.D.,

E.R. Sutherland, M.D., Ph.D., is Director of the Diabetes

Institute for Immunology and Transplantation and Head of the

University of Minnesota Division of Transplantation. Regarded as the

pioneer of pancreas transplants, Dr. Sutherland and his associates

have performed more than 900 pancreas and islet transplants during

his 30-year quest to perfect a cure for diabetes. Many of the doctors

who trained as residents and fellows under his direction have gone on

to develop pancreas transplant programs around the world. While his

achievements have brought him numerous awards and honors, Dr.

Sutherland is known among his patients as a man of great humility who

is always available to answer their concerns and who is determined to

give back to them the quality of their days.

http://www.diabetesinstitute.org/people/sutherland.htm

The Diabetes Institute For Immunology and Transplantation Department

of Surgery 420 Delaware Street, SE Minneapolis, MN, 55455 Phone: (612)

624-8402 Website: http://www.Diabetesinstitute.org

[Guest guest]

The invention of the automated method of islet isolation by Camillo

Ricordi, M.D., the DRI's Scientific Director, made it possible for

scientists to obtain larger numbers of islets from a human pancreas.

Islets only form about 2% of the entire pancreas, and isolating them

from the rest of the pancreas that does not produce insulin takes

approximately 6 hours. Further improvements on the Ricordi method

have made it possible to isolate enough islets from one pancreas to

transplant one patient. Until recently, as many as 5 and 6 organs

were needed to carry out one transplant, making the advent of this

automated method a major step forward in the field.

Despite this advance, however, the demand for islets still exceeds

the currently available supply of organs. So scientists are looking

for ways to develop alternate sources of islets through genetic

engineering, islet expansion and regeneration, and perhaps in the

near future, from sources such as pathogen-free animals.

Start the islet cell isolation process below to learn how it's done,

and then view actual footage from an islet cell transplant in

progress.

Primary non-function is a poorly understood phenomenon and describes

islets that either never functioned or that lost their ability to

function very early in the post transplant period. Current studies

are under way at the DRI to determine if using different combinations

of reagents in the separation and isolation phases of islet

processing can reduce the incidence of early islet loss. Another

investigative approach involves studying the microenviroment of the

liver into which the transplanted islets are introduced. The focus

here is on two types of liver cells believed to be critical in the

earliest inflammatory responses seen after islet transplant.

Overcoming early graft loss could help make islet transplant success

rates comparable to that of solid organs. Islets that survive this

early phase have been shown to function for as long as seven years

after transplant, proving that islets can function for a long time

once transplanted.

Acute rejection usually occurs in the first 6-12 months after

transplantation and chronic rejection, more often than not, is a

biopsy confirmed finding after the first post-operative year.

Currently, rejection is kept somewhat in check through the life-long

use of powerful anti-rejection medications, called

immunosuppressors.

Researchers worldwide are attacking the rejection problem from

several directions. At the DRI, scientists are leading the

initiative by bringing the latest immunomodulatory interventions from

the field of organ transplantation to bear on the problem of

diabetes. Read about these newest agents capable of modifying immune

system reactions below, explore the role of bone marrow and how these

multiple avenues of research are being fast-tracked into patient

trials as soon as this year. The goal is make the transplant

recipient's immune system unresponsive to the " foreign " islets. In

other words, to make the patient " tolerant " to the donor cells.

Today's immunosuppressive drugs are the standard way of preventing

rejection after a transplant.

The human body's ability to recognize and eliminate something

that " does not belong, " is one of its greatest forms of protection.

The cells responsible for distinguishing between what is " self " and

what is " non-self " belong to the immune system and constitute a

formidable and complex police force. Finding ways of safely

sidestepping these hardworking law enforcers are at the cornerstone

of DRI's work in transplant immunology.

Rejection of a cell/organ can take several

forms: " hyperacute " , " primary non-function " , " acute " , " chronic " ,

and " autoimmune recurrence. "

Healthy islets (center) surrounded by non-insulin producing pancreas

tissue.

Xenotransplantation researchers at the DRI have made headway in

identifying the red-flag markers present on pig islet cells, for

example, that are believed to signal " non-self " to our immune

system. Although the human body has naturally occurring antibodies

that recognize pig islets as 'foreign' and cause hyperacute reaction,

researchers are studying this species as a potential donor because of

its anatomic (size) and physiological (function) similarities to

man. Understanding where the telltale pig islet markers lie and how

this signaling works is the first step in being able to make porcine

islets a more viable transplantation option in the future.

Insulitis: Islets (center) are being infiltrated as they undergo

immune system attack.

Hyperacute rejection is a severe reaction that is seen within minutes

of transplantation. Antibodies in the recipient's bloodstream are

able to quickly identify and react against the transplanted organ or

cells, resulting in graft failure within hours of the procedure.

These types of reactions are the rule in transplants performed across

species, and are one of the obstacles that must be overcome before

non-human sources of islets can become reality.

But prolonged use of these drugs leads to serious side effects,

including infections and cancer, making them a less than ideal

solution to the rejection puzzle. They are also not foolproof, with

each rejection episode leading to the loss of some of the

transplanted islets and a slimmer chance of achieving insulin

independence.

[Home page] [science Made Simple] [DRI Scientists at Work] [speed

the Progress]

Contact DRI

Disclaimer

Copyright © 1998-2004 Diabetes Research Institute Foundation

3440 Hollywood Blvd, Hollywood, FL 33021

1- tel. fax

This site is supported by the DRIF

Address & Regional Offices

The success of any transplant depends on the degree to which the

recipient's immune system can be driven to do the unnatural -

" accept " a " non-self " tissue. Tissue typing so that the donor's

and recipient's most important markers of " self " are as similar as

possible is one way of improving the odds of a transplant's success.

The best matches are between identical twins and the next best are

between close relatives, such as brothers and sisters. The other

approach is to lull the recipient's immune system into a more

unresponsive state. Traditional immunosuppressors, such as steroids

or cyclosporine, produce a system-wide decrease in immune system

efficiency, but come with many unwanted side effects.

Today, DRI scientists are attempting to achieve tolerance that is

specific to the donor (donor-specific tolerance) without having to

suppress the entire immune system. Armed with the latest advances in

diabetes research, they are using bone marrow cells taken from the

donor, combining the newest immunomodulatory agents, and designing

novel ways of determining chimerism – the co-existence of donor and

recipient immune cells within the recipient's body. Studies suggest

that being able to induce a state of chimerism may be important -

maybe key - to establishing donor-specific tolerance and maintaining

a successful transplant over time.

Cells that are destined to become immune system cells, like T cells

and B cells, are produced in the bone marrow, the spongy lining of

the vertebrae and long bones. DRI researchers have processed more

than 500 bone marrow harvests in the Cell Transplant Center and their

most recent studies have shown that delayed infusions of these cells

significantly improve both patient and graft survival in liver

transplants. Now pre-clinical studies are being conducted to

translate this important clinical finding to the field of diabetes.

DRI researchers have already helped develop a rapid selection method

for isolating certain stem cells from the bone marrow harvests.

Through collaborations with various biotechnology companies, the DRI

team is now able to expand these key cells on a large enough scale to

go to clinical trial. Multiple grants have been awarded to the DRI,

enabling scientists there to refine these advances in the area of

tolerance, and bring their latest results to clinical trials in 1998.

[Guest guest]

What are islet cells?

Islets are pancreas cells that are able to sense sugar in the blood

and release just the right amount of insulin to maintain normal sugar

levels in the body. Islet cells comprise only 1% to 2% of the total

number of cells found in the pancreas, and are scattered throughout

this organ. When viewed through a microscope, they look like small

clusters of islands (or isles) floating in a sea of other pancreas

cells.

Can you get enough islet cells from one pancreas?

Until recently, multiple organs were needed to obtain sufficient

numbers of islets to do one transplant. Improved technology has

allowed researchers to isolate enough human islets from a single

donor pancreas to perform a transplant. But results vary and depend

on the expertise of the team performing the isolation.

What type of procedure is required to transplant islets?

Islets are transplanted very similarly to the way an intravenous

(I.V.) drip is given. It is not considered a major surgical

procedure. After the patient receives local anesthesia and is put

under light sedation, a catheter (small tube) is inserted into the

portal vein through a needle inserted just below the rib cage. The

islets then drip to the liver, where they lodge and begin to function

on their own.

How long can transplanted islets last?

In 1990, the DRI performed what has now become the longest successful

human islet cell transplant to date, reversing diabetes in a select

group of patients who had also received a simultaneous organ

transplant (for complications unrelated to diabetes). Although these

patients required some insulin and immunosuppression to prevent

rejection, they were able to maintain normal blood sugar levels

without episodes of hypoglycemia (low blood sugar reactions). For

years, DRI researchers have shown that transplanted islet cells can

function for more than eight years.

Can a family member donate islets?

No. Currently, islet cells are obtained only through the organ donor

program. Therefore, those who have met untimely deaths and have

willed their organs for transplantation are the source of islet cells

used in our clinical trials. A variety of strategies are underway

however, to develop other cell sources for the future.

Why, until now, have islet cells been transplanted only in

conjunction with another organ?

o prevent the rejection of transplanted organs or cells, recipients

must take immunosuppressive or anti-rejection drugs. These drugs put

patients at risk for infections and a host of other debilitating

conditions. Researchers feel that the risk of these drugs outweighs

the potential benefit of improved glucose control, or even of the

reversal of diabetes. Therefore, patients suffering from end-stage

kidney disease, for example, who were receiving a new kidney were

eligible to receive islets since they would need to begin

immunosuppressive therapy anyway.

It has always been the DRI's goal to perform islet cell transplants

before the development of diabetes-related complications, and to do

this without the need for long-term immunosuppressive drugs.

How can immunosuppression be eliminated?

The DRI has been studying the use of bone marrow infusions from the

same donor as a way to induce tolerance, or " trick " the recipient's

body into recognizing the transplant as " self. " Preliminary trials

with liver and kidney transplant patients receiving donor bone marrow

have produced very encouraging results. The decrease in organ

rejection observed in the majority of these procedures using bone

marrow has enabled DRI scientists to move forward and test islet cell

transplants together with the donor bone marrow in patients with

diabetes.

Where does bone marrow come from?

The bone marrow must come from the same organ donor as the pancreas.

The goal here is to establish " donor-specific " tolerance in the

recipient so that he or she will not have to take anti-rejection

medication for life. Tolerance means that the immune system does not

react against something and try to remove or destroy it - in this

case, the donor's cells.

[Guest guest]

let me know if that helps.....if you need something more, please let

me know...I hope this finds you and yours well...Mark