peter rathjen stem cell therapies – and the future of medicine
TRANSCRIPT
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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