Clinical islet Clinical islet transplantationtransplantationStephanie A Amiel, BSc, MD, FRCP

RD Lawrence Professor of Diabetic MedicineKing’s College London School of Medicine

Diabetes Research Group

Treatment of organ failure?

• Renal failure

• Liver failure

• Heart failure

• Islet failure

• Kidney transplant

• Liver transplant

• Heart transplant

INSUU100

Case Histories

1. Born 1944; T1DM 1966; keen runner

2. Born 1965; T1DM 1987; HCA on locked ward

3. Born 1985; T1DM 1994; mother of two

“afraid to be in charge of my granddaughter”

“threatened with medical redundancy”

“you just drove across a red light, Mummy”

GLUCOSE-GLUCOSE-RESPONSIVERESPONSIVE

INSULIN DELIVERYINSULIN DELIVERYBionics vs nature?

Nature – whole pancreas or islets?

Islet TransplantationIslet Transplantation• 1998 established laboratory• 2000 proof of concept• 2002 1st UK patient• 2008 NCG funded programme

Insulin Independence, Insulin Dependence, Graft failure

*C-peptide data not available at Day 75

**Year 3 status independent of re-infusion

CITR Islet Alone Recipients outcomeFrom all infusions

Recipient Status Insulin IndependentInsulin Dependent with Detectable Fasting C-peptideNo Detectable Fasting C-peptideMissing Data

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

Month 6N=249

Year 1N=225

Year 2N=169

Year 3N=129

No severe hypoglycemic episodesSevere hypoglycemic episodeMissing data for recipient without islet graft functionMissing data for recipient with islet graft function

Per

cent

of R

ecip

ient

s

0

10

20

30

40

50

60

70

80

90

100

Pre Inf 1N=262

Day 30N=262

Month 6N=249

Year 1N=225

Year 2N=169

Year 3N=129

CITR 2007

SEVERE HYPOGLYCEMIA FOLLOWING LAST TRANSPLANT

• 1 person with 4% reduction in HbA1c• 2 people back in work• 1 woman resumed running and

babysitting her grandchildren• 2 children safely back on school run

• 3 people achieved insulin independence

Clinical Outcomes: Diabetes UK patients

UK ITC

Shaw, Manus, Amiel, Huang

NCG:April 20082 isolation centres6 Transplant centres

Intractable hypoglycaemiaIslet after kidneyLocal and remote

Problems to be solved

• Current• Organ supply/distribution• Sub-optimal immunosuppression

• Research• Prevent loss of islets on administration• Improve immunosuppression• Make new islets to give greater loads and

re-transplant if required

Meanwhile

• Whatever cell therapy we devise, it will need to be safer than insulin therapy

• For a small number of patients, it already is