Download ES cells

Molecular Medicine
Molecular Medicine
Stem cell therapy
Gene therapy
Tumor therapy
Immunotherapy
Other therapies
Vaccines
Genetic diagnostics
Medical genomics
Therapy
Diagnostics
B0
medicine: old desire to replace damaged tissues
B1
B2
- They can give rise to every cell type  zygote and 8-cell embryo
zygote
Inner cell mass
- They an give rise to every cell type, except, trophoblast tissues
 blastocyst inner cell mass
Trophoblast cells
- They can give rise a limited type of cells  adult stem cells
ES cells
Cardiac muscle cells
Skin cell
- They can divide, but they are able to give rise cells identical with themselves
- neurons, skeletal muscle cells, cardiac muscle cells:
Neuron
B3
Unipotent
Non-dividing
skin cell
neuron
pigment cell
Zygote is totipotent
sperm cells
Germline
cells
ectoderm
zygote
blastocyst
egg cell
gastrula
brain
eye
Inner cell mass
totipotent
pluripotent
multipotent
blood
liver
mesoderm
endoderm
Bone marrow
skin
cardiac-, skeletal musle cells
tubulue cell
red blood cells
smooth muscle cell
alveolar cells
pancreatic cells
thyroid cells
muscle
B4
Brain
Umbilical cord
blood
Neural stem cell
Glial cells
neurons
Hematopoetic stem cell
Red blood cells
Platelets
mezenchymal
White blood cells cells
B5
B6
A
A
A: adult stem cells
A
A
P
P: progenitor cells
D: differentiated cells
P
D
P
D
B7
2007
Mouse stem cells (1981)
Martin Evans
Gail R. Martin
In vitro fertilization
Nuclear transfer
enucleated
egg
nucleus
donor
nucleus
egg cell
5 day embryo
Tissue compatibility
innner cell mass (ICM)
Es cells
B8
B10
adipocyte
neuron
Inner cell mass
macrophage
Blastocyst
Cultured
ES cells
Smooth muscle cell
Glial cell
1. In vivo differentiation: implanting directly to the body
2. In vitro differentiation, and then implanting to the body
B11
zygote
B12
Nuclear reprogramming
(epigenetic reprogramming:
loose of commitment)
Somatic nuclear transfer
B13
Reprogramming is simple, since
these cells are not differentiated,
but their isolation is difficult
Germ line nuclear transfer
B17
In vitro fertilization
sperm
Egg cell
zygote
morula
blastula
ES cells
Multipotent stem cells
Differentiated cells
Transplantation
B18
Egg cell
Nuclear transfer
Nucleus from a somatic
cell of patient
zygote
morula
blastula
ES cells
Multipotent stem cells
Differentiated cells
Transplantation
B19
Hematopoetic stem cells
Cultured stem cells
Transplantation
Leukemia patient
Myeloid progenitor cell
In the body of patients
Blood cells
Multipotent cells (reduced potency)
Hematopoetic cells
Hematopoetic stem cells
differentiation
NK cell T lymphocyte Neutrophil granulocyte
Lymphoid progenitor
cell
hematopoetic
Stem cell
Bazophil granulocyte
B lymphocyte
Eozinophil granulocyte
Monocyte
Multipotent
Platelets
Stem cell Myeloid progenitor
cell
Red blood cells
odipocita
osteocytes
Stromal cells
They protect hematopoetic cells
B20
Hematopoetic stem cells
Use in medicine
(1) Bone marrow (from 1950’s): the only successful stem cell therapy
- Medication:
◊ leukemia
◊ sickle cell anemia
◊ immune deficiency
◊ bone marrow damages
◊ some metabolic disorders
- Unpleasant intervention
- Successful if the donor and recipient are genetically similar
(2) Umbilical blood and (3) placenta blood (new discovery):
- Use: medication of the donor person decades after the isolation or the
medication of relatives
Bone
marrow
B21
B22
B23
Genetic manipulation
Smooth- and cardiac muscle
cells, endothelial cells
in vitro differentiation
Blastocyst
TRANSPLANTATION
Heart progenitor cells
Heart
(embryonic or adult)
TRANSPLANTATION,
in vivo differentiation
Smooth- and cardiac muscle
cells, endothelial cells
B24
Burn injuries:
Traditional treatment – skin transplantation from undamaged body parts, success, since stem cells
are located directly under the epidermis. If there were not enough skin, the patient could die.
Since 20 years – cultivation of skin stem cells
Discovery of new skin stem cells – in deeper layers of skin and in hair bulbs
epidermis
dermis
hypodermis
Neural stem cells (NSC) neurogenesis in adult brain
SVZ
SVZ
Olfactory bulb
NSC
NSC
hippocampus
cerebellum
hippocampus
HUMAN BRAIN
Anterio-lateral chamber subventricular zone (SVZ)
RAT BRAIN
New neurons
B25
B26
Parkinson’s disease
- Those neurons that are responsible for the elimination of
unnecessary movements, are degenerated at the substantia nigra 
implantation of stem cells has not been proven to be successful
B27
Spinal cord damage
Broken
bone
Spinal cord
damage
B29
Éva Mezey
Y chromosome
B30
BLOOD CELLS
ADIPOCYTE
EPIHELIAL CELL
CARDIAC MUSCLE
NEURON
GLIAL CELL
Stromal (mesenchymal) stem cells in the marrow
B32
5 day embryo
STOP
B31
Stromal cells
Mesenchimal stem cells (MSC; stromal stem cells)
-Not only structural role, but a role in tissue regeneration, too.
Sources:
- Bone marrow, umbilical cord blood, fat tissue
Doubts:
it is possible that stromal cells only fused with other cell types instead
of differentiating to other cell types.
MSC: mesenchymal stem cells = marrow stromal cells
B33
Singapore - Biopolis
B33
He changed the „stem cell law” at the very first 24 hrs
B34
Basic research:
generation of knock-out animals
Medical research:
drug tests
Medicine:
medication:
- Testing the cells of sick patients
- Leukemia, Parkinson- and disease, neural damage, seizure, cardiac disease, diabetes
Real applications:
- Leukemia, skin regeneration, heart attack
B14
Cell reprogramming
Mouse iPS cells (2005)
Transfer of fibroblast cells to feeder cells
Transformed cells
Delivery of iPS factors-encoding
genes by retrovirus vector
iPS cells
Skin fibroblast cells
Some cells are transformed
to iPS cells
iPSC: induced Pluripotent Stem Cells
Shinya Yamanaka
B15
Cell reprogramming
iPSC: induced Pluripotent Stem Cells
36
What and how to deliver?
András Nagy
Somatic cells
Transcription factors
Integrating Non-integrating
virus
vector
Excisable
vector
Protein
Small molecules
37
Transcription factors
Pluripotent cell
Multipotent cell
Differentiated cell
B28
Genetic improvement
by homologous recombination
41
From adult stem cells or iPSC
biopolymer
Problems:
vasculature, innervation
Video on ear printing:
https://www.youtube.com/watch?v=dlOoCVogyfQ