2. Fact
t Shee – Wha
et 1 – at are
e Stem lls
m Cel
Stem cells
s are stirring up great exc
citement in m
medical rese
earch. What are they and
d why are scientists so
intrigued by them?
What ar
re stem cells?
The huma an body is made up of ab bout 200 diff ferent kinds o
of specialised cells such aas muscle ce ells, nerve cells,
fat cells and skin cells. All specialis
sed cells orig
ginate from s
stem cells. A stem cell is aa cell that is not yet
specialiseed. The proceess of specialisation is ca lled differentiation and oonce the diffferentiation pathway of a a
stem cell has been decided, it can no longer b ecome another type of c cell.
Different types of stemm cells have different lev vels of poten
ntial. A totipo
otent cell has s the capacitty to form ann
entire org
ganism includ ding the emb bryo and the e placenta. Human develo opment beg ins when a s sperm fertiliz
zes
an egg and creates a s single totipot the first hours after fertilization, this cell divides into identica
tent cell. In t al
totipotentt cells. Appro
oximately four days afte r fertilizationn and after several cycles s of cell divis
sion, these
totipotentt cells begin to specialize
e.
A stem ce
ell that can become every y type of celll in the body
y including a new embryo o and placenta is called
t. A stem cel
totipotent ll that can be
ecome every y type of cell in the body, apart from a new embryo and the
placenta, is called pluripotent and d a stem cell that can bec
come only sp pecific group
ps of cells is c
called
multipote
ent.
Where are stem cells foun
nd?
Stem cells s are found in the early eembryo, the f foetus, amniotic fluid, th
he placenta a and umbilica al cord blood.
After birthh and for the
e rest of life, stem cells c ontinue to re
eside in man ny sites of thee body, incluuding skin, ha
air
follicles, b
bone marrow w and blood, brain and sp pinal cord, th
he lining of the nose, gut t, lung, joint fluid, muscle
e,
fat, and mmenstrual bloood, to name e a few.
Factsheet
t 1 – What a
are Stem Cells? Pa
age 2
5. range of b
blood disorders and imm mune system conditions ssuch as leuka
aemia, anaem mia and autooimmune
diseases. Once collectted, cord blo
ood can be st
tored in a cord blood ban
nk for future
e use as a pot
tential sourc
ce of
stem cells
s for transpla
ant.
Pluripo
otent Ste
em Cells
Embryo
onic Stem
m Cells
Discovereed in the mou and in huma ns in 1998, h
use in 1991 a human embr ryonic stem c
cells (hESCs) are the mos
st
primitive type of stem
m cell and can
n replicate a nd generate every cell ty
ype of the hu
uman body.
Human em
mbryonic ste
em cells are dderived fromm human blastocysts (ear rly stage emb bryos) that aare five to seven
days old. In the e UK these bblastocysts ar
re donated f for research with consent
fro
om patients w who have co ompleted treeatment for iinfertility, annd have surplus
em
mbryos. At th his stage of d
development t the blastocyyst is a hollo
ow ball of abo out
1550 cells and nno bigger thaan a pinhead. Figure 1 de emonstrates the different
parts of the bla astocyst, sho
owing that next to a large e internal cavity (C), is a
sm
mall group of f approximately 30 cells ccalled the inn
ner cell mass s (ICM). The
ouuter layer is t
the trophectoderm (T).
The inner cell m
mass is what
t ultimately b
becomes the
e embryo, an
nd the
Figure 1 ‐ H
Human Blastocy
yst tro
ophectodermm becomes the placenta. The inner ce ell mass cells
s are able to
de
evelop into a ny type of ceell in our bod
dy and can coontribute to all the cells and
tissues of the adult or
rganism. The
ese types of c
cells are calle
ed pluripotent and it is th ency that makes
his pluripote
them of innterest to research and t
therapy. Embbryonic stemm cells are isoolated from tthe blastocyst when the
inner cell mass is removed and cultured in thee laboratory. During this process the blastocyst iss destroyed.
Once the cells have be een isolated they can be grown continuously in a a laboratory culture dish that containns a
nutrient‐rrich culture m
medium. As tthe stem cel ls divide andd spread over the surface e of the dish some are
removed to populate fresh subcul ltures to form
m a stem cel ability to keep
ll line. Because these cellls have the a
dividing (s
self‐renewing), large nummbers of em bryonic stem m cells can be e grown in th
he laborator ry and also
frozen forr future use. Therefore, e
established hhESC lines caan be maintained in labor ratories for r
research, shaared
between researchers and maybe u ultimately ussed in cell‐ba
ased therapies.
Somatic
c Cell Nuc
clear Tran
nsfer (SCN
NT) or Therapeutic
c Cloning
SCNT refe
ers to the rem
moval of a nuucleus, which h contains thhe genetic mmaterial or DNNA, from virttually any ce
ell of
the body and its trans
sfer by inject
tion into an uunfertilised eegg (oocyte) from which the nucleus has also bee en
removed. The newly r reconstitutedd entity is th en stimulate ed to start dividing. After
r 5‐7 days in culture,
embryonic stem cells can then be removed an nd used to cr reate many e embryonic st tem cells in c
culture. Thes
se
ines are gene
embryonic stem cell li etically identtical to the c
cell from which the DNA w was originally removed.
SCNT may y have applic
cations in the f embryonic stem cells w
e creation of which can the en be used fo or the
developm ment of patient‐ and diseaase‐specific c herapies as w
cell‐based th well as the prroduction of f stem cells wwith
specific di
isease characteristics for
r research pu
urposes. The use of a pat tient's own ccells for tissue replaceme ent
through SSCNT may ov vercome the problem of iimmune reje ection that is
s a major commplication of f tissue or or
rgan
transplanttation today
y.
SCNT is co
ommonly ref ferred to as t
therapeutic ccloning. The word ‘clonin
ng’ often connjures up images of cloni
ing
an individ
dual (reprodu
uctive cloning) such as th
he process ussed to create
e Dolly the sh
heep. Using SCNT to creaate a
Factsheet
t 2 – Types o
of Stem Cells age 5
Pa
6. human em mbryo to impplant into a u
uterus is illeg
gal in the UK
K and many pparts of the w
world. The sc cientific
communit ty overwhelmmingly rejectts reproduct tive cloning, but SCNT ma
ay provide an n invaluable tool for basic
research. However, w whilst the technology has been proven in many sp yet to produ
pecies it has y uce a stem ce
ell
mans. A major breakthro
line in hum ough occurre ed in November 2007 wh hen a group o of scientists reported tha
at
they had ssuccessfully extracted stem cells from m monkey embryos gene erated by SC CNT.
Induced
d Pluripotent Stem
m Cells (iP
PS)
In Novem
mber 2007, a significant development occurred wh hen scientist
ts
announceed they had d
developed a new techno ology to cause mature human cells
to resemb
ble pluripote
ent stem cells
s similar in m
many ways too hESCs. These
reprogram
mmed cells aare referred t
to as induced d pluripoten
nt stem (iPS) cells.
Initially iP
PS cells were generated u using viruses to geneticallly engineer mature
cells to acchieve a pluripotent statu us. The purp pose of the viirus was to innsert F
Figure 2 ‐ Human iPS Cells
reprogram mming genes s into a cell s
such as a skinn cell and the
en culture th he cells in
the labora atory for 4‐5 weeks after r which a sm all number o of iPS cells be
egin to appe ear. However r technologiees
for reprog gramming ce ells are moving very quic kly and resea archers are n now investig gating the use of new
methods t that do not rremain in the e cells causin
ng permanen nt and poten ntially harmfuul changes. T These new
technolog gies currentlyy utilise diffe
erent types o of non‐integrrating viruses and chemic cals and sma all moleculess.
Similar to SCNT, this technology allows scientiists a new method of creating disease ed cells for r
research by uusing
mature ce ells from a pa
atient with a
a genetic dise
ease, such ass Huntingtonn’s disease, a
and turning t those cells in
nto
iPS cells. S
Such diseasee‐specific stem cells may enable diseaase investiga
ation and druug developm ment offering g a
unique op pportunity too recreate booth normal aand diseased human tissu ue formation n in the laboratory. iPS
technolog gy also has th
he potential to produce ggenetically id
dentical “pat
tient specific
c” embryonic c stem cell‐like
lines that would be re ecognised as “self” and n ot rejected bby the patien
nt they were e made from. However th here
is much to o be underst tood before tthis could be
e achieved.
Whilst the e discovery o
of iPS cells is a significant
t breakthrou ugh in the field of reprogrramming, the use of iPS c cells
in the clin
nic is many ye
ears away ‐ if it occurs at t all ‐ as seve
eral significan
nt hurdles neeed to be overcome. It is s still
unclear ho ow genetically stable or safe iPS cells s will be for ppotential clin
nical use. Moore research needs to be e
done into o induced pluuripotent stem cells to di scover if the ey will offer t
the same equ uivalent rese
earch value a as
embryonic stem cells. . Having only y recently disscovered the ese cells, scie
entist are yet
t to confirm if iPS cells ha
ave
y to divide an
the ability nd remain ch hromosomal ly stable like e embryonic stem cells ov ver a long pe
eriod of time e.
Factsheet
t 2 – Types o
of Stem Cells Pa
age 6
7. Fact
t Shee
et 3 – Umbi
ilical C
Cord Blood
d Stem
m Cell
ls
Umbilical cord blood i is a rich sour
rce of stem c
cells that are a type of
adult stemm cell. With t
the consent of the paren nts, blood can be
collected from the um mbilical cord of a newbor rn baby short tly after
s does not hu
birth. This urt the baby or the moth her in any wa ay, and it is
blood that would othe erwise be disscarded as bbiological wasste along
with the pplacenta (anoother rich soource of stem
m cells) after the birth.
Umbilical cord blood s stem cells arre haematop poietic stem ccells
similar to those foundd in the bone e marrow, wh hich can be uused to
generate red blood ce ells and cells of the immuune system. Cord
blood stem cells may even have th he potential to generate other non‐b blood cell typ
pes but more
e research is
required.
Cord bloood stem cells are currentl
ly used to tre
eat a range o
of blood diso
orders and immmune systeem condition ns
such as le
eukaemia, annaemia and aautoimmune e diseases. Th
hey are used largely in th
he treatment
t of children but
have also started bein
ng used in ad
dults followinng chemothe erapy treatm
ment.
Umbilic
cal cord b
blood banking in th
he UK
Blood fromm the umbilical cord is riich in stem c
cells and can be collected d stored in a cord blood
d at birth and
bank until it is require
ed by a patient. Cord bloood can be freeely donatedd to the publlic cord bloo
od bank where it
is availabl
le to any individual who needs it and d is the correct tissue ma
atch; or a priv
vate bank foor the exclusi
ive
use of thaat donor for a fee.
Public c
cord bloo
od banking.
In the UK the public coord blood ba ank is run by the NH. By d
donating you mbilical cord blood it can then
ur child’s um
be used fo or a potentia
ally lifesaving
g transplant for a patient
t in need. A p
patient requ iring a stem cell transpla
ant
would be treated with h stem cells f from the sammple most closely matching their own n tissue type
e. Along withh this
strong network, the p process undertaken by th he public ban nking system ensures rigo orous screenning procedu ures.
There are e now over 3000,000 units s registered w
worldwide fo or public use, increasing t
the chances that a suitab ble
unit will b
be found whe en needed. T There is no c ost involved for the donation to a puublic cord blo
ood bank.
For more information see http://w
www.nhsbt.n
nhs.uk/cordb
blood/
Private
e cord blood bankin
ng
There is a
also the option to store c
cord blood in
n private cord blood banks. Private coord blood coollection and
storage seervices are generally available across
s UK for an upfront cost a
and yearly fe
ees. Unlike p
public cord b
blood
banking, tthe cord bloood stored in private bank
ks can only b
be released for the exclussive use of th
he donor.
However it is worthwhile noting that if the do nor developed a blood c cancer such aas leukemia a and requiredd a
transplantt in the futur
re, their own
n stored cord
d blood may not be ideal as there is a troducing the
a risk of reint
disease.
Informatio
on on private banks can be found by
y asking your
r doctor or th nline search.
hrough an on
Saviour
r Siblings
Controver rsy has arisen over the practice of ge
enetically selecting embryos created during infert tility treatme
ent,
for the puurpose of using the donor baby's cord d blood to tr
reat a matched ill sibling.. In this procedure, genet tic
testing is performed t to ensure thaat the embryyo will provid
de cord blood devoid of t the genetic ddefect afflicting
Factsheet
t 3– Umbilic
cal Cord Bloo
od Stem Cel
lls Pa
age 7
9.
Fact
t Shee
et 4
uced Pluri
Indu ipotent Ste
em Cells (
(iPS c
cells)
Stem cell science is ann extremely f fast moving ffield of resea
arch with new breakthro oughs being reported alm most
daily. This
s swiftly chan
nging landscape has seen n many different stem ce ell types and technologiees capture
popular immagination including embryonic stem m cells (ES ceells), tissue st
tem cells andd cord bloodd stem cells.
Currently attracting a lot of public c attention a re some rece ent breakthr roughs in the programming
e areas of rep
and in parrticular the d
discovery of a way to ma ke a new ste em cell type which have b been named d induced
pluripotennt stem cellss (iPS cells).
Reprog
gramming
g
The term reprogramm ming is often used to refe er to techniques developed by scient tists to chang
ge the
developmmental potential or fate oof a cell. The
e objective off reprogrammming is to ta ke a definedd cell from th
he
body (som
matic cell), su
uch as a skin cell, and connvert it to m
more primitive
e stem cell w
which would be capable o of
developin
ng into anoth her cell type such as a heeart or blood cell.
Induced
d Pluripotent Stem
m Cells
In Novemmber 20071, 2a
a significant d
developmen nt occurred w when scientis
sts announce ed they had developed a a
new technnology to cause mature h human cells to resemble e pluripotent stem cells s
similar in many ways to
hESCs by altering the gene activity
y within the cell. These re
eprogramme ed cells are r
referred to as induced
pluripoten
nt stem (iPS)
) cells.
PS cells were generated u
Initially iP using viruses to genetical
lly
engineer mature cells s to achieve a
a pluripotentt status. The purpose
of the viru us is to insert reprogramming genes into mature cells such
as skin cells. The cells are then gro own in the la
aboratory for r several
weeks aft ter which a small number of iPS cells begin to app pear.
However technologies ramming cellls are moving very
s for reprogr
quickly an nd researche ers are now investigating the use of n
new
methods t that do not u use viruses w
which can ca use permanent and Figure 3: iPS C
Cell Colon
potentially harmful ch hanges in thee cells.
What co
ould iPS c
cells offer
r?
If they ar
re able to be made safely y, and on a la
arge scale, iP
PS cells could
d possibly havve the same therapeutic
c
potential as any form of pluripote ent stem cell,, providing a source of ceells for replac
cement and regeneration
after dammage due to d disease, injur
ry, congenitaal (birth) def
fects or norm
mal ageing.
This techn nology also a
allows scientists a new m
method of cre eating diseas
se specific ce
ells for research by creatiing
iPS cells fr
rom the adult cells of a p
patient with a
a genetic dis
sorder, such as Huntingtoon’s disease. . Studying th
hese
1
Yu J, Vody
yanik MA, Smmuga‐Otto K, AAntosiewicz‐Bo ourget J, Franne JL, Tian S, N
Nie J, Jonsdotttir GA, Ruotti V
V, Stewart R,
Slukvin II, T
Thomson JA. IInduced plurippotent stem c cell lines deriv
ved from human somatic ce ells. Science, 2
2007, vol 318,
pp1917‐2.
2
Takahashhi K, Tanabe K,, Ohnuki M, N
Narita M, Ichis saka T, Tomod da K, Yamanak ka S.. Inductio
on of pluripoteent stem cells from
adult huma an fibroblasts
s by defined fa
actors. Cell. 20
007, vol 131(5 5), pp861‐72.
Factsheet
t 4 – Induced Pluripoten
nt Stem Cell
ls (iPS Cells)
) Pa
age 9
12.
Types of stem cells ‐ jumbled task
The following table outlines the types of different stem cells and provides information about each one. The
only problem is that the information is all jumbled up. Cut out the row and column headings and paste them
into your workbook. Next, cut out each information cell and place it under the correct column and in the
correct stem cell row. Arrange the cells in your book first and check your work before you paste them down.
Type of stem cell Where do they The cells they Scientific Drawbacks of
come from> are able to make advantages of these stem cells
these stem cells
A) Pluripotent B) Due to the D) Small numbers
C) Usually only the E) Any cell in the
stem cells pluripotent nature found in tissue,
type of cells or body
E.g. embryonic they also carry a difficult to locate.
tissue that it is
stem cells (ESC), risk of cancer if not derived from Usually only
induced treated properly generates the cell
pluripotent stem before transferred types of the tissue
(iPS) cells, somatic to a patient. in which they are
cell nuclear As ESCs are not found.
transfer patient specific With the exception
(SCNT) stem cell treatments using of cord blood and
them may trigger bone marrow only
rejection by the small numbers are
patient’s immune found in tissue,
system. difficult to locate.
Only generate the
cell types of the
tissue in which they
are found. Usually
difficult to grow
outside the body in
large numbers.
F) Multipotent G) Can be grown in H) They are capable I) ESC – Derived J) Undifferentiated
adult stem cells large quantities in of limited from human cells found in
E.g. cord blood the laboratory. Can selfrenewal. Use in blastocysts (early tissues and organs
cells, adult stem be manipulated to research is less stage embryos)
cells such as skin grow into different controversial. No about 5–7 days old.
stem cells, muscle cell types in the tissue rejection if iPS cells – derived
stem cells laboratory. cells derived from from
iPS and SCNT – the patient. reprogrammed
these cells are an somatic cells, such
identical match to as a skin cell.
the somatic cell SCNT stem cells –
donor and can be derived from
used to study cloned blastocyst
disease and avoid made from a
immune rejection reprogrammed
somatic cell and
enucleated eg
Types of Stem Cells Page 12
14.
Find out more
Disease
Who are affected
What cures/
treatment can we
offer today?
How do scientists
think stem cells
might help
What type of stem
cell and why?
How do they hope
to use the stem
cells?
When do they
think they will be
able to offer a
treatment/cure?
What problems do
they scientists
have to
overcome?
Find out more Page 14
16.
Common acronyms and glossary
ART Assisted reporductive technology ICM Inner cell mass
ASC Adult Stem cell IVF In Vitro Fertilisation
CIRM California Institute for Regenerative hESC Human embryonic stem cell
Medicine
EMA European Medicine Agency iPS Induced Pluripotent Stem
ESC Embryonic Stem Cell MHC Major histocompability complex
FDA Food & Drug Administration MHRA Medicines and Healthcare products
Regulatory agency
GvHD Graft vs host disease MSC Mesenchymal stem cells
HLA Human leukocyte antigen NIH National Institutes of Health
Adult stem cell (also known as tissue stem cell) means undifferentiated cells found in the tissues and organs
of the body. They are capable of self‐renewal. Their differentiation is mainly restricted to forming the cell
types of that tissue or organ. The chief role of adult stem cells is to maintain and repair the tissue in which
they are found.
Allogeneic transplantation is a cell, tissue or organ transplant from one individual to a genetically different
person.
Autologous transplantation is a cell, tissue or organ transplant from one individual back into the same
individual. Such transplants are often performed with blood products or bone marrow and do not induce an
immune response and are not rejected.
Blastocyst is an early stage embryo about 5–7 days post fertilisation containing about 150 cells and is the size
of a pinhead. A blastocyst consists of two types of cells: the inner cell mass cells, from which embryonic stem
cells are derived and which gives rise to all the organs and tissues of a future embryo and foetus; and the
trophoblast which forms a portion of the placenta.
Cell based therapy is a treatment that involves stem cells being induced to differentiate, or develop, into
specific cell types required to repair or rebuild depleted cell populations or tissues.
Cellular differentiation is when an unspecialised cell becomes specialised into a specific cell type.
Cell division is the process by which one cell divides into two cells, thereby increasing the cell population.
Differentiation is the process whereby an unspecialised (undifferentiated) cell develops into specialised cells
such as those in the liver, brain or heart.
Efficacy is the capacity to produce an effect.
Embryo is the conceptus developed from the fertilized egg (zygote) until it becomes a foetus, which in the
human, is approximately eight weeks later.
Embryonic stem cells come from a 5–7 day old blastocyst (early embryo). They have the ability to form
virtually any type of cell found in the human body, but are not capable of developing into a whole new
organism.
Ethics Committees review all aspects of a proposed research project and determine whether the proposed
research is ethical. Research involving animals, humans or human tissue require ethics approval. If the
Committee do not think it is ethical, they can stop the scientist from performing his or her research.
Common Acronyms and Glossary Page 16
17.
Foetus is the conceptus that follows the embryo stage and develops till birth and displays the characteristics
of the adult species.
Graft vs host disease (GvHD) is a complication that can occur after a bone marrow transplant in which the
newly transplanted material attacks the transplant recipient’s body.
Haematopoietic stem cell (HSC) is a type of cell that make blood cells, it is the parent cell or ‘precursor’ of
mature blood cells and are found in adult bone marrow, umbilical cord blood, peripheral blood and foetal
liver.
HTLV-1 – Human T‐Lymphotropic Virus Type I (HTLV‐1) is a human RNA retrovirus that causes T‐cell
leukaemia and T‐cell lymphoma in adults and may also be involved in certain demyelinating diseases,
including tropical spastic paraparesis.
Induced pluripotent stem cells (iPS cells) are derived from mature/differentiated cells of the body by
reprogramming through genetic manipulation, to which resemble the pluripotent embryonic stem cells. The
reprogramming technology is changing rapidly.
In vitro fertilisation (IVF), achieved outside the body, is an assisted reproduction technique where the egg
cell and the sperm cells are brought together in a dish (i.e. in vitro), so that the sperm can fertilise the egg. The
fertilised egg, a zygote, will form the embryo which can then be implanted into the womb for establishing
pregnancy.
Mesenchymal stem cell is a type of adult stem cell found in several tissues of the body including bone
marrow and the placenta which can give rise to a number of tissue types such as bone, cartilage, fat tissue,
and connective tissue. Mesenchymal stem cells have shown promise for treatment for a number of diseases.
Multipotent is the potential of an individual stem cell to develop into a restricted number of (but not all)
types of cells. Adult stem cells are examples of multipotent stem cells.
Peer review is the process of subjecting an author’s scholarly work, research, or ideas to the scrutiny of
others who are experts in the same field.
Pluripotent is the ability of the stem cell to develop into many types of cells in the body. ES and iPS cells are
examples of pluripotent stem cells.
Precursor cell is a cell that gives rise to other cells. A precursor cell is less specialised than other cells. If a
painting was a specialised cell, the precursor cell would be the canvas.
Progenitor cell is a transitional form of stem cell that can differentiate, but can no longer renew itself.
Progenitor cells are restricted to the generation of a few types of specialised cells.
Somatic Cell Nuclear Transfer (SCNT) refers to the removal of a nucleus, which contains the genetic
material or DNA, from virtually any cell of the body and its transfer by injection into an unfertilised egg
(oocyte) from which the nucleus has also been removed. The newly reconstituted egg is then stimulated to
start dividing. After 5–7 days in culture, embryonic stem cells can then be removed. These embryonic stem
cell lines are genetically identical to the cell from which the DNA was originally removed. To date, SCNT has
not been used to create a human embryonic stem cell line.
Stem cell is an unspecialised/undifferentiated cell with the ability to renew indefinitely and to produce
specialised cell types in the body.
Common Acronyms and Glossary Page 17
18.
Stem cell line refers to stem cells that have been established and propagated in culture and maintained
consistent characteristics and potential.
Stem cell tourism/medical tourism is when a patient chooses to seek treatment in another country, either
for cost or availability reasons. Virtually every type of health care, including plastic surgery, orthopaedic
surgery, reproductive treatments, psychiatry, alternative treatments, convalescent care and dentistry are
available. Some medical travel is simply a means of getting access to a widely accepted treatment at a cheaper
price, or for unproven treatments generally not offered in a patient’s home country. Many patients opting for
these treatments do so because they feel they have no other alternative treatments available.
Tissue stem cell (also known as adult stem cell) means undifferentiated cells found in the tissues and
organs of the body. They are capable of self‐renewal. Their differentiation is mainly restricted to forming the
cell types of that tissue or organ. The chief role of adult stem cells is to maintain and repair the tissue in which
they are found.
Totipotent refers to the cells within a 1–4 day embryo. Each cell of an embryo at this stage can theoretically
make a whole new individual.
Common Acronyms and Glossary Page 18
