Peter Rathjen Stem cell therapies – and the future of medicine

Peter Rathjen

Stem cell therapies – and the future of medicine

Mammalian embryogenesis

Embryonic Stem (ES) Cells

Blastocyst

ICM(stem cells)

Isolate ICMCulture in vitro

(+LIF)

ES Cells

Properties of ES cells in vitro

Blastocyst

ES Cells

ImmortalPluripotent

Differentiate

Unlimited numbers, of any kind of cell

Differentiated Cells

Cell Therapies

“An unlimited supply of any kind of cellwith any genetic modification”

Cell replacement: Parkinson’s disease (nerves)Stroke (nerves)Heart disease (muscle)Diabetes (pancreas)Immune system (blood)Blindness (Retinal cells)

Gene therapies: Thalassemias (blood)Dystrophies (muscle)

Cell Therapy with ES cells: how it will work

Somatic cell biopsy

Master cell bank

ES cell

+

+

Transplant intopatient

Cell product

Differentiation

NucleusEnucleated oocyte

EnucleatedES cell

Patient

Donorembryo

∂ ∂

Human neurons from human ES cells

Differentiation

HumanES Cells

Neurons

Cell Therapy with ES cells: how it will work

Somatic cell biopsy

Master cell bank

ES cell

+

+

Transplant intopatient

Cell product

Differentiation

NucleusEnucleated oocyte

EnucleatedES cell

Patient

Donorembryo

ES cell-derived neurons in vitro

Neurons identified by expression of the neural marker, tubulin- III

neurectoderm

ICM

Mesoderm Endoderm

Origin of Ectodermal Lineages in Mammals

6.5 d.p.c.

ectoderm

primitive ectoderm

PNS CNS

neural plate

neural tube

4.5 d.p.c.

5.5 d.p.c.

PL

UR

IPO

TE

NT

EC

TO

DE

RM

AL

surfaceectoderm

hair

skin

+BMP4

Cell Therapy with ES cells: how it will work

Somatic cell biopsy

Master cell bank

ES cell

+

+

Transplant intopatient

Cell product

Differentiation

NucleusEnucleated oocyte

EnucleatedES cell

Patient

Donorembryo

Integration of ES cell-derived neural precursors in the adult brain

ES cell derived cells in the rat striatum, 16 weeks after injection

Correction of disease models

Drug induced Parkinsonian model(neural precursors/neurons)

Spinal cord lesions(neural precursors)

*Immune deficiency(bone marrow/gene correction)

*genetically modified stem cells

Insulin deficiency(insulin producing cells)

Cell Therapy with ES cells: how it will work

Somatic cell biopsy

Master cell bank

ES cell

+

+

Transplant intopatient

Cell product

Differentiation

NucleusEnucleated oocyte

EnucleatedES cell

Patient

Donorembryo

Oocyte donor(Scot. Blackface)

AnimalCloning

Enucleation

Natural

Birth

CLONED ANIMAL

Oocyte donor(Scot. Blackface)

AnimalCloning

Enucleation

Surrogate “mother”(Scot. Blackface)

SurrogateMother

Nucleus donor(Finn Dorset)

Insert Mammary Gland Nucleus

Oocyte donor

Enucleation

Somatic cell biopsy

ES cell

++

Nucleus

EnucleatedES cell

SCNT/Therapeutic Cloning: Overcoming Rejection

Somatic CellBiopsy

Fibroblast ‘pluripotent’ cell

Inject into mouse blastocyst

Contribution to all germ layers

Inject under mouse skin

Cell Dedifferentiation: Overcoming Rejection

KLF4

Sox2 c-mycOct4

Cell Therapy with ES cells: how it will work

Somatic cell biopsy

Master cell bank

ES cell

+

+

Transplant intopatient

Cell product

Differentiation

NucleusEnucleated oocyte

EnucleatedES cell

Somatic cellbiopsy

Nucleus

+

Enucleatedoocyte

+

EnucleatedES cell

nuclear reprogramm

ing

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