Pancreatic Islet Cell Transplantation

For
Type-1 Diabetes

Under the guidance of :

Dr.G.Sudhakara rao sir,
M.Pharm,Ph.D

Presented by:
Narendra Bhupati Naidu.B
06431R0037
Phase-I
 WHAT IS DIABETES??
 TYPES OF DIABETES
 SYMBOL OF DIABETES
 CAUSES OF TYPE-1 DIABETES
 SYMPTOMS OF DIABETES
 WHAT IS ISLET CELL TRANSPLANTATION?
 PANCREATIC ISLET CELLS
 NEED FOR ISLET CELL TRANSPLANTATION
 GOAL OF ISLET CELL TRANSPLANTATION
 Phase II
 Differences
 Why islets are preferred to pancreas?
 Who is eligible for islet transplant?
 Who is a good donor?
 Procedure
 Procurement-suitable and not suitable
 Complications with procedure and immunosuppressants
 Possible reasons of islet graft failure
 Hurdles
 Future aspects
 Conclusion
 References
 Differences
Pancreas transplant
 Pancreas obtained from
cadaver donors, transplanted
surgically within 12 hours
 Surgical procedure involves
general anesthesia, abdominal
surgery, and a 7-10 day
hospitalization
 Complications:
 Thrombosis of pancreatic
vessels
 Pancreatic leak
 Infection
Islet Cell Transplant
 Islet tissue obtained from
cadaver organs by collagenase
digestion of the pancreas and
purification of islets via density
gradients
 Islets injected into portal vein for
liver implantation, performed by
interventional radiology, followed
by a 1-2 day hospitalization
 Complications:
 Bleeding
Why islet cells are preferred to pancreas??

 It involves a minor surgical procedure.

 Less expensive

 A mere 1-2 days hospitalization is enough

 Probably safer
Who is eligible for islet transplant?
 Type 1 Diabetes Mellitus for >5 years. 18-60 yr of age.

 Hypoglycemia unawareness (glucose <3.0mmol/or 54 mg/dl)

 Metabolic liability/instability (hypoglycemic or

ketoacidosis(>2 hospital<12mo)

 chaotic glucose profile (>6.6 mmol/l or 120mg/dl)

 Progression 2o to complications despite optimal insulin

regimen

 failure of intensive insulin management, as judged by an

independent endocrinologist.
Who is a good donor??
• Age: 15 to 50 yrs,

• History: Absence of type 1, type 2 and gestational

diabetes, pancreatic
trauma, sepsis, treated or active tuberculosis, active viral encephalitis,
rabies, malignancy other than primary brain tumours, dementia, and
high-risk behaviour

• Circulation: Cardiac arrest with CPR or pulse loss for ≤ 15

minutes
and hypotensive episodes are only considered exclusion criteria.

• Serology: Negative for HIV-I, HIV-II, HTLV-I, HTLV-

II, HBsAg, anti-HBs
PROCEDURE
 The procedure of islet cell transplantation mainly
involves two steps:

1.Isolation of islets from a deceased donor.

2.Transplanting the islets to the patient.

Procurement – Suitable for Transplantation

On arrival After trimming Intact islets

rocurement –not suitable for transplantatio

Excess fat Blood inside Fragmented islets

parenchyma
Isolation of islets...
 Highly purified enzymes such as collagenase is used to isolate
islets from the pancreas of a deceased donor.

 This enzyme solution is injected into the pancreatic duct

which runs through head,body and tail, which causes
distension of pancreas.

 Then it is cut into small chunks & transferred to Ricordi’s

chamber, where digestion takes place until the islets are
liberated and removed from the solution.

 Isolated islets are then separated from the exocrine tissue and
debris in a process called purification.
Ricordi’s chamber Final islet preparation
Transplantation...
 During the transplant, a radiologist uses ultra sound
and radiography to guide placement of a catheter
through the upper abdomen and into the liver.

 The islets are then infused through the catheter into

the liver.

 It takes time for the islets to attach to new blood

vessels and begin releasing insulin.
Complications with procedure...

 Bleeding
 Heamoperitonium
 Hemothorax.
 Right portal vein thrombosis
 Reduced vascular perfusion to transplanted islets
MINOR:
 Serum sickness
 candidiasis
Complications with immunosuppressants

 Expensive
 May increase risk for specific malignancies and
opportunistic infections
 Some drugs like Rapamycin are also known to
impair normal islet function
 Side effects such as oral ulcers, peripheral edema,
anemia, wt. loss etc
 Some drugs such as Calcineurin inhibitors are
nephrotoxic
Hepatic Steatosis following
islet transplantation
 Possible reasons of islet graft failure

Insufficient islet mass Poor quality of islets

Failure to engraft
Toxicity of anti-
rejection drugs
Insulin resistance Islets
Disease recurrence
Allograft rejection
Hurdles to successful islet
transplant..
 Limited supply of human islet tissue

 Adverse effects of immunosuppressive protocols

 Technical factors

 Immune mediated destruction

 Recurrence of autoimmune destruction

Future avenues in islet
transplantation!
 Develop strategies to improve viability of insulin producing
tissues

 In vitro expansion of human islet and beta cell (fetal

pancreatas)

 Genetically engineered non-islet or human cell lines

 Stem cells

 Xenotransplantation

 Tolerance Induction
Conclusion..
 Successful islet cell transplantation is now possible
which is less invasive and less complicated than
pancreas transplants...!

 But innovations in inhibiting early inflammations and

reducing the toxicity of medicines is needed..!

 Organ allocation, patient selection, and payment for

islet transplantation will remain controversial topics
during the “growth” phase of development of islet
transplant programs
References...
 ^ Lakey J, Burridge P, Shapiro A (2003). "Technical aspects of islet
preparation and transplantation". Transpl Int 16 (9): 613–632. doi:
10.1111/j.1432-2277.2003.tb00361.x. PMID 12928769. 
 ^ Close N, Hering B, Eggerman T (2005). "Results from the inaugural
year of the Collaborative Islet Transplant Registry". Transplant Proc 37
(2): 1305–1308. doi:10.1016/j.transproceed.2004.12.117.
PMID 15848704. 

WEBSITES:
 http://www.surgery.wisc.edu/patients/txislet01 overview.
html
 www.pubmed.com
 www.wikipedia.org
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