Cloning & stem cell strategies in transplantation

Robert Lanza, MDVP Medical & Scientific DevelopmentAdvanced Cell Technology

Adjunct ProfessorInstitute for Regenerative MedicineWake Forest University School of Medicine

Alzheimer ’s

Dwarfism

Parkinson ’s

Strokes

Epilepsy

Hemophilia

Kidney failure

Chronic pain

CancerInfertility

Burns

AIDS

Muscular dystrophy

ALS

Affective disorders

Macular degeneration

Hypoparathyroidism

Heart disease

Liver failure

Enzymatic defects

Diabetes

Osteoarthritis

Multiple sclerosis

Huntington ’s

Hypocholesterolemia

Rheumatoidarthritis

Atherosclerosis

Ulcers

Spinal cord injuries

10

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100

1988

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2001Year

Num

ber

of P

atie

nts (

in th

ousa

nds)

Waiting List

Organs Transplanted

2001

2003 [First stem-cell stage SCNT embryos]

Lanza et al Science 2000Lanza et al Science 2000

0.0

20.0

40.0

60.0

80.0

0.0 1.0 2.0 3.0 4.0 5.0 6.0

A

.

Telomere fluorescence (in kMESF)

0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0

Dupl. 1Dupl. 2

Exp. 1 Exp. 2

Young cattle5-10 mos old

Old cattle> 10 yrs old

Newborn calves< 2 wks old

Cloned cattle5-10 mos old

10 20 30 40 50 60 70 10 20 30 40 50 60 700 80

Cy= - 3.62 x + 61.8

R2 = 0.54

B

Years

kMES

F

23.1

9.4

1 2 3 4 5 6 7 8 9 10

Mean TRF 18.3 15.2 20.1 18.3 15.2 20.1 14.4 16.4 12.1 16.1

kb

0

20

40

60

80

100P

OP

ULA

TIO

N D

OU

BLI

NG

S

NORMAL FETUS CLONED FETUS

•Parkinson’s ($6 billion/yr)

•Stroke ($45 billion/yr)

•Spinal cord injury ($10 billion/yr)

•Epilepsy ($3 billion/yr)

•Alzheimer’s ($100 billion/yr)

•Multiple sclerosis ($10 billion/yr)

Production of new hES lines that will be safe forclinical applications

• Feeder-free system• Serum-free system• Elimination of all

animal products,including sialic acids

• Generated using goodmanufacturingpractice (GMP)

A B

C D

E

G H

I

L

F

A B

C D

E

G H

I

L

F

Generation of ES cells using parthenogenesis

Retinal Degenerative Diseases

• Age-related macular degeneration (ARMD) alone affects over 30 million people worldwide• Leading cause of blindness in patients over 60 yrs old in the US• Degeneration of retinal pigment epithelium (RPE) plays a critica l

role in the pathogenesis of AMRD as well as retinitis pigmentosaand other retinal degenerative diseases

• Transplanted RPE cells have been shown to rescue host photoreceptors and attenuate loss of visual function in animals

• Stem cell -derived RPE could be a potentially important source of tissue for subretinal transplantation in patients

WBC colony from cloned stem cells

•Cardiovascular disease costs the US $329 billion annually

End-stage renal disease will cost US $1 trillion during the comingdecade