Islet Transplant

7/30/2019 Islet Transplant

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Principles of Pancreatic

Islet Transplantation

Saptarshi Bhattacharya

Medical College Kolkata


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Diabetes mellitus is a very common medical

condition with immense medical, social and

financial costs

One of the leading causes of kidney failure,

blindness, non traumatic amputations, and

impotence


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Discovery of

insulin by Banting

and Best in 1922

changed diabetes

from a lethaldisease to chronic

illness


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Even withmost stringent

insulinregimensmicrovascularsequelae will

occur in over50% ofdiabetics.


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A successful

pancreas

transplant can

establish

normoglycaemiawith glucose

control similar to

nativefunctioning

pancreas


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Pancreatic transplant is a major surgery

requiring complex vascular reconstruction

Many of the complications seen with whole

organ pancreas transplant are due to the

exocrine component which actually is

useless component


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Thus the concept

of cell

transplantation isvery logical and

attractive


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Report of 7consecutive successful

human islet transplants

by Shapiro et al at theUniversity of

Edmonton in 2000 has

ushered in a new era in

this field (NEJM

343:230-238, 2000)


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Isolation of islets

Islets account for 2% of intact pancreas

Automated method of isolation described by

Ricordi and coworkers


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Enzymatic digestion

by collagenase

Islets and small

contaminating exocrinetissue fall at the bottom

agitation

Islets separated by

density gradient

Yields islets of 50 to 90 % purity

centrifugation


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Site of transplantation

Peritoneal cavity

Subcutaneous or intramuscular

Spleen

Renal subcapsular space

Immunologically privileged sites likeanterior chamber of eye, brain, pregnant

uterus placenta


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The livervia portal

vein embolization isthe commonest site

Dual vascular supply

allows embolizedislets to occlude portal

venules without

infarction


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Technique

OPD procedure

Portal vein

innoculated by

trancutaneous

transhepatic route

Cannulating the

umbilical vein


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Complications

1) Percutaneous hepatic

puncture

2) Portal venous thrombosis3)DIC

Portal venous pressure

monitoring

Islets in heparinised

solution


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Immunosuppression

Islet celltransplantation per seis not a lifesaving

procedure to warrantlifelongimmunosuppression

Commonly employedimmunosuppresivedrugs arediabetogenic


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Immunosupression

Edmonton protocol

No corticosteroids

Induction by anti IL2 receptor

antibody

Maintenance with

combination of low dosetacrolimus and sirolimus

Multiple infusion of islets


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Graft failure

Lack of reliable marker for early graft

rejection

Hyperglycemia late indicator


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Graft failure

T lymphocyte mediated

rejection

Damage by autoimmuneprocess of diabetes

Primary dysfunction


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Some strategies

Pretransplant storage ofislets in tissue culturereduced immunogenicityby depleting passengerleukocytes

Maintenance of normal

blood glucose levels inimmediate post transplantperiod


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The future

Microencapsulation or

surrounding islets with

semipermeable membrane

Allow small molecules like

oxygen & glucose to enter

cells and insulin to exit

Protect from immune cells and

antibodies


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The future

Xenogeneic islet cells(Porcine islet cells)

The immunological barrier toxenogeneic grafts issubstantiallygreater than thebarrier to human grafts

The developmentoftransgenic pigs that expresshuman genes


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The future Pancreatic ductal epithelial cells

from adult non-obese diabetic micethat are still prediabeticcan be

grown in long term cultures andinduced to produce functioning

islets.

Capable of lowering blood glucose

concentrations to near normal whenimplanted in diabetic non-obese

mice.


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The future

Fetal pancreatic stem

cells and cell

precursors Embryonic stem cells

and therapeutic cloning


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Where we stand?

Despite initial failures pancreatic islet

transplantation has gained momentum and

presently at several centers the one year

results are comparable with whole pancreastransplantation


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At the present time, clinical application of

islet transplantation should be limited to

clinical trials, focusing on techniques toenhance islet engraftment and survival.


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Documents

Islet Transplant