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Stem Cell Therapy – A Panacea for all Ills?
Rajgopal L
Journal of Postgraduate
Medicine,
Seth GS Medical College
& KEM Hospital,
Mumbai-400 012, India
Correspondence:
Rajgopal L
[email protected]
PubMed ID
: 16333185
J Postgrad Med 2005;51:161-3
ecently, a team of South Korean scientists has enabled a paraplegic of 19 years to walk after
injecting stem cells derived from a cloned embryo into the site of spinal cord injury. It has
been shown in an adult mouse with myocardial infarction that bone marrow stem cells are able to
differentiate into cardiac myocytes, endothelial cells and vascular smooth muscle cells. [1]
Intracoronary infusion of autologous bone marrow stem cells in patients with acute myocardial
infarction has been shown to decrease the functional myocardial defect and increase the left ven­
tricular ejection fraction.[2] Allogenic mesenchymal stem cell grafts are seen to regenerate bone in
dogs without the need for immunosuppressive therapy.[3] Apart from these, stem cell therapy seems
to hold promise in a variety of conditions like Type I diabetes, Parkinson’s disease, amyotrophic
lateral sclerosis, hepatic degeneration, corneal surface defects and much more – so much so that it
has spawned a new speciality of medical practice “Regenerative Medicine.”
R
Stem cell therapy has been in vogue in the form of bone marrow transplantation for several years
now. What has given an impetus to this field is the isolation of
human embryonic stem cells from the inner cell mass of blas­
tocyst by James Thomson in 1998.[4] Stem cells are broadly
categorized into Embryonic Stem Cells (ESCs) and Adult or
Somatic Stem Cells (SSCs). ESCs can be derived in two ways:
from embryo formed by the fusion of sperm and ovum and as
of now such embryos are available as excess embryos from in­
vitro fertility (IVF) clinics. The second method is through
therapeutic cloning using Somatic Cell Nuclear Transfer
(SCNT) technique, wherein the nucleus of a somatic cell is
injected into an enucleated ovum, which then starts dividing
like an embryo. This was the technique used by the South
Korean scientists.
Adult stem cells are found in the mature, terminally differen­
tiated tissues and are of two types: Haematopoietic Stem Cells
(HSCs) and Mesenchymal Stem Cells (MSCs). Haematopoi­
etic stem cells in the bone marrow are the oldest known vari­
ety of stem cells. HSCs are also found in the peripheral blood,
umbilical cord blood and fetal hematopoietic system. MSCs
are found in the bone marrow (as stromal cells), umbilical cord
matrix (as perivascular cells of Wharton’s jelly), placental tis­
sue, fetal tissue, fat and muscle. A sub-population of MSCs
known as Multipotent Adult Progenitor Cells are also identi­
fied in the bone marrow.[5] Multipotent adult stem cells, also
known as basal cells, have been known to exist in the basal
layer of epidermis of skin and in the lining epithelium of
gastrointestinal tract and respiratory tract and in the epithe­
lium of the limbus (sclero-corneal junction). These cells usu­
ally regenerate and replace cells that are lost to maturation
and senescence.[6] More recently, the discovery of stem cells in
the post-mitotic tissues, thought to be incapable of regenera­
tion, like brain (in the hippocampus and in the subventricular
zone), myocardium and skeletal muscle has opened up excit­
ing new possibilities.[7]
J Postgrad Med September 2005 Vol 51 Issue 3
Embryonic Stem Cells Versus Adult Stem Cells
Both embryonic stem cells and adult stem cells are capable of
indefinite self-renewal; are capable of differentiation into spe­
cific functional cells and tissues and are capable of homing to
areas of inflammation and injury.[5] Their capacity to replicate
indefinitely both in vivo and in vitro is a boon to regenerative
medicine. Adult stem cells in skin, GIT, limbus etc. while dif­
ferentiating into specified functional cells, replicate to pro­
tect their number, thereby maintaining a constant pool. Stem
cell turnover and differentiation should always be in balance.
If replication is not adequate, it may lead to stem cell defi­
ciency at these sites.
ESCs are pluripotent and are capable of differentiating into
tissues derived from any of the germ layers i.e. ectoderm or
mesoderm or endoderm. This ‘Proteus’ like quality of ESCs
can be used to manipulate them using tissue engineering tech­
niques to develop new organs. MSCs also show pluripotency
by differentiating into many tissues and also into tissues to­
tally different from that of their origin. This capacity of
transdifferentiation of MSCs into adipocytes, chondrocytes,
myocytes, osteocytes, glial cells and neural cells makes them
ideal for stem cell therapy.[8] Maintenance of MSCs and their
differentiation are controlled by their particular micro-envi­
ronment, where chemical cues may be playing a role.[9] Stem
cells exhibit different markers on their surface which helps in
distinguishing their type.
The Scope of Stem Cell therapy
The homing of stem cells to areas of tissue injury or inflam­
mation may occur via a chemical route. This characteristic of
stem cells can be used to treat tissue defects. Tissue necrosis
releases certain chemical factors or signals that cause chemo161
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Rajgopal: Stem cell therapy
taxis and mobilize stem cells to the site of injury. Based on the
same principle MSCs have been used as gene carriers by intro­
ducing exogenous DNA into them. Viral transduction using
adenoviruses in stem cells can generate stable clones and may
be used in gene therapy. Stem cells can similarly may be used
in drug delivery systems.[7,11]
In yet another application of stem cells, multipotent adult pro­
genitor cells may be turned into pluripotent stem cells similar
to ESCs. This is developmental backtracking or rewinding
known as ‘dedifferentiation’ and these pluripotent stem cells
may then be used in therapy.[12] Another remarkable aspect of
stem cell therapy is the immunoprivilege enjoyed by the ESCs.
Allogenic ESCs do not evoke an immunological reaction after
transplantation. In fact, they are said to induce immunologi­
cal tolerance for organ transplantation and may obviate the
need for immunosuppressive therapy.[13]
pathogens.[18] Many governments like European union, have
now made it mandatory that isolation and expansion of stem
cell lines are done according to proper guidelines and in con­
cordance with Good Manufacturing Practices.[19]
If we search the history of Medicine, we find that man has
always tried to treat diseases with available materials starting
from herbal plants, metals and metallic compounds and then
antibiotics and anti-viral agents. While the former two treated
the symptoms, the latter two tackled the causative agents.
Where these did not have a scope, he resorted to manual in­
tervention in the form of surgery. Having expanded his knowl­
edge in molecular medicine and cell biology, it is only a correct
step that he should resort to cell-based therapy trying to es­
tablish the original milieu by almost re-creating the original
cells in lieu of the diseased ones. But while trying to play God,
he cannot become God himself and hence the caution required
in going ahead full steam with Stem Cell therapy.
Ethical Dilemmas
The use of ESCs is however mired in the ethical controversy
of destruction of the embryo while harvesting ESCs. Some
argue that it is equivalent to killing a baby to take out the cells
/organs to save other people’s lives. Since they believe that
ensoulment occurs at conception, they oppose embryonic stem
cell therapy. Yet, there are people like Sandel who believe oth­
erwise. He compares human embryo to an acorn; acorns grow
into oak trees. He says, in spite of the developmental continu­
ity, acorns and oak trees are different structures. Similarly, non­
sentient human embryo is different from sentient human be­
ing according to him.[14] There are yet others who argue that of
the two sources of ESCs, a product of therapeutic cloning is
just that – a product manufactured with the sole purpose of
harvesting ESCs. McHugh calls such a product as a ‘clonote’
as opposed to a ‘zygote’ formed by the fusion of sperm and
ovum for reproductive purpose.[15] Use of allogenic or autolo­
gous MSCs or HSCs will circumvent this ethical controversy
easily. But they have to be expanded (cultured) in numbers
before use and their plasticity i.e. differentiation potential is
less than that of ESCs. Another problem they face is that of
immunogenicity because HSCs and MSCs are not as
immunoprivileged as ESCs and hence use of allogenic MSCs
and HSCs would require immunosuppression.
Presently, the questions facing stem cell therapy are:
i. What type of stem cell to use? - ESC or HSC or MSC?
ii. When and by what route to administer? – After conven­
tional treatment fails or concurrently?- Whether to inject
intralesionally or intravascularly?
iii. In what manner to use them? As basic stem cells or after
transdifferentiation / tissue engineering?
The answers will not be immediately forthcoming. Still there
is a lot of ground to be covered. Stem cell therapy has to be
pursued with caution taking care of ethical concerns and in­
herent biological and logistical problems. Yet, stem cell therapy
holds open one promising door where all else have been closed
and it is hoped, a few years hence, stem cells will occupy a
pride of place in the therapeutic armamentarium.
References
1.
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3.
4.
Apart from ethical problems, ESC therapy also faces some bio­
logical problems. ESCs have a tendency to form teratomas and
also exhibit chromosomal abnormalities. If the ESCs are ob­
tained from therapeutic clones, the problems faced by cloned
mammals due to senility of cells will also plague this form of
therapy.[16] To produce a therapeutically cloned embryo, the
South Korean scientists had to waste 250 oocytes. Thus there
is also the fear of dehumanizing practices like embryo farms,
commercialization of oocyte donation etc.[17] Maintenance and
expansion of ESCs are presently done on feeder cell layer like
mouse embryonic fibroblast layer. Such exposure to animal cell
lines carries a risk of contamination with retroviruses and other
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Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, et al. Bone
marrow cells regenerate infracted myocardium. Nature 2001;410:701-5.
Chen S, Fang W, Ye F, Liu Y, Qian J, Shan S, et al. Effect on left ventricular
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Rajgopal: Stem cell therapy
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Rajgopal L
Journal of Postgraduate Medicine,
Seth GS Medical College & KEM Hospital, Mumbai-400 012,
India. E-mail: [email protected]
Forthcoming Symposia
Journal of Postgraduate Medicine will be publishing symposia on important public health issues
such as Telemedicine and Disaster Medicine. Watch out for the articles from the experts in the
field.
Health Issues of Disasters
• Disasters as complex medical emergencies - F. M. Burkle Jr
• Planning in the warning phase of disaster - R. W. Perry
• Pre-hospital response for disaster: the role of information communication technology J. L. Arnold
• Preparing for the man-made disasters: Bioterrorism - D. A. Alexander
• Medical management of disasters - V. Kvetan
• The post-disaster effects: The psychological impact - D. Silove
J Postgrad Med September 2005 Vol 51 Issue 3
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