CELL THERAPY

STEM CELLS

AIM:

REPLACE FUNCTIONALLY INCOMPETENT

AND/OR DEAD CELLS,
WITH NEW, EFFICIENT ONES

ADULT STATE - CELL RENEWAL SYSTEM

stem cells - proliferation and differentiation
rapid turnover -blood cells,
epithelial cells, gametes

proliferation of existing differentiated cells

(pancreatic cells, liver cells, endothelial cells)

Some cells - nerve cells, heart muscle cells, sensory

EMBRYONIC STEM CELLS

ADULT STEM CELLS
INDUCED PLURIPOTENT STEM CELLS

BASIC DEFINITIONS

STEM CELLS undifferentiated cells that are

capable of self-renewal for indefinite period and
have ability to give rise to differentiated cells

PROGENITOR CELL - cell in fetal or adult

tissue which is an ancestor of a particular cell

PRECURSOR CELL - cell in fetal or adult

tissue which immediately precedes a
particular cell

stem cell progenitor cell precursor cell

differentiated cell

BASIC DEFINITIONS

EMBRYONIC STEM CELL - primitive

(undifferentiated) cell from the embryo that has
the potential to differentiate to various
specialized cell types
ESC is pluripotent !

ADULT STEM CELL - an undifferentiated cell

found in a differentiated adult tissue than can
renew itself, and can differentiate to all
specialized cell types of the tissue from which it
originated
(and some others !) Many ASC are multipotent

NOBEL
2007
STEM
CELLS

BASIC DEFINITIONS

TOTIPOTENT CELL - cell able to give rise to

all cell types of the body and of the embryonic
membranes

PLURIPOTENT CELL - cell able to give rise to

all cell types of the body

MULTIPOTENT CELL - cell able to give

rise to more than one differentiated cell
type

ZYGOTE

TOTIPOTENT

MULTIPOTENT
CELLS

8-cell
embryo

TOTIPOTENT
BLASTOMERS

BLASTOCYST
Embryoblast
Inner cell mass

PLURIPOTENT
CELLS

Differentiated
cell

BASIC DEFINITIONS -

PLURIPOTENT CELLS

EMBRYONIC STEM CELL

EMBRYONIC GERM CELL - cell found in a

specific part of the embryo/fetus called the
gonadal ridge that normally develop into mature
gamete

EMBRYONAL CARCINOMA CELLS a pluripotent stem cells which appear either in

spontaneous, usually testicular tumors, or as a
result of transplantation of stem cells in
heterotopic tissue

Stem cells: scientific progress and future research directions.

NIH - June 2001

EMBRYONIC STEM CELLS

Stem cells: scientific progress and future research directions.

NIH - June 2001

ESC propagation

ESC maintaining as
undifferentiated cells

Stem cells: scientific progress and future research directions.

NIH - June 2001

Nature 2001, 414, p. 93

ESC differentiation

Isolation and
separation of
differentiated
cells

Nature 2001, 414, p. 95

Insulin-secreting
pancreatic-like
cells obtained
from ESC

Stem cells: scientific progress and future research directions.

NIH - June 2001

SOMATIC THERAPEUTIC CLONING

Fusion
and cell activation

Enucleated oocyte

Somatic cell nucleus

Nucleus

Oocyte
Somatic cells in Go

In vitro culture

Embryonic stem cells

ADULT STEM CELLS

STEM CELL NICHES

ADULT STEM CELLS

PLASTICITY

MUSCLE STEM CELLS

(Satellite cells)

Satellite cell

Expression of MRF
myogenic regulatory factor

myoblasts

myotube
Basal lamina

muscle
fiber

Muscle-derived
stem cell

Myogenic

Osteogenic

Adipogenic

Chondrogenic

Hematopoietic

BONE MARROW STEM CELLS

HEMATOPOIETIC STEM CELLS

STROMAL STEM CELLS

HEMATOPOIETIC STEM CELLS

MESENCHYMAL STEM CELLS

Mesenchymal stem cells (MSC)

Bone marrow stromal
Umbilical cord
Cord blood
Peripheral blood

Connective tissue
Adipose tissue
Trabecular bone
Synovial fluid

Muscle
Amniotic fluid

Placenta

Mesenchymal stem cells (MSC)

Avoid allogeneic rejection in humans and in animal models
1. MSC are hypoimmunogenic (often lacking MHC-II and costimulatory molecule
expression)
2. Prevent T cell responses (directly- disrupting NK and CD8 and CD4 T cell
function; indirectly- modulation of dendritic cells)
3. Induction of suppresive local microenvironment (production of prostaglandins
and IL-10)

Potential interactions between MSC and neural cells in CNS

(iPSC) INDUCED
PLURIPOTENT STEM CELLS

INDUCED PLURIPOTENT STEM CELL - IPSC

adipocyte

c-Myc, Klf4, Sox2, Oct4

iPSC

neuron
macrophage
smooth muscle
cell

fibroblast
p53
Oct4, Sox2

others

RUDOLF YAENISH - 2007

NOBEL
INDUCED
2012
PLURIPOTENT
STEM
CELLS - IPSCs

Sir John B. Gurdon

Shinya Yamanaka

THERAPEUTIC GRAFTING
and

TISSUE ENGINEERING

Bone and cartilage

engineering

Genetic modification
(expression of anti-tumor
mediators)
Bone tumors

MSC injected;
systemically,
locally

Examples engineered tissues

Biopsy of somatic
cell / stem cells

direct
implantation
into new niche
- cell reprogramminig
in vivo

enucleated
oocyte

nucleus

in vitro culture
4-blastomeres
embryo

in vitro
differentiation
into new cell
type

in vitro grown
blastocyst

transplantation

in vitro
differentiation
into new cell
type

isolation and culture

of embryonic stem
cells

NEURAL STEM CELLS

embryonic stem cell

multipotent stem cell

neural stem celll

Glial progenitor cell

neural progenitor cell

oligodendrocyte
progenitor
cell

astrocyte
progenitor cell

neuron
oligodendrocyte

astrocyte

transgene

transgene carrier

transgene

transgene carrier

Patients cells

Genetic modification
and cells culture

TRANSGENE
Gene inserted into DNA helix
and able to transcribe

Stem cells: scientific progress

and future research directions.
NIH - June 2001

Porwnanie pluripotencjalnych komrek macierzystych myszy, mapy i czowieka

Mysie komrki
EC/ES/EG

Marker

Mapie
komrki
ES

Ludzkie komrki
ES

Ludzkie komrki
EG

SSEA-1

SSEA-3

SEA-4

TRA-1-60

TRA-81

Oct-4

Aktywno telomerazy

+ ES, EC

nieznana

Alkaliczna fosfataza

nieznana

Zaleno od
warstwy odywczej

ES, EG,
niektre EC

Tak

Tak

Czynniki wpywajce
na samoodnow

LIF i inne
czynniki
dziaajce
poprzez
receptor pg130

Hodowle
z warstw
odywcz

Warstwa odywcza
z surowic ,
warstwa odywcza
bez surowicy +
medium + bFGF

ES - Embryonic stem cell

EG - Embryonic germ cell
EC - Embryonic carcinoma cell

nieznana ?

Ludzkie komrki
EC

+
+
Tak

LIF, bFGF
forskolina

SSEA - Stage - specific embryonic antigen

TRA - Tumor rejection antigen -1
LIF - Leukemia inhibitory factor

niepena

Nie znane
niska zdolno
proliferacyjna

Regenerative medicine
Skin regeneration
Blood vessels
Liver
Bone regeneration
Cartilage regeneration
-Skeletal muscles
-Cardiac muscle
-Cornea; retina
- cells of Langerhans islets