Stem cells are
primitive cells that give rise to other types of cells. Cell therapy
using stem cells is a group of techniques, or technologies, that rely on
replacing diseased or dysfunctional cells with healthy, functioning ones.
These new techniques are being applied to a wide range of human diseases.
The commonest stem cell therapy that the physician is familiar with is
bone marrow transplant. Cord blood being a rich source of stem cells,
there is increasing interest in the storage and use of cord blood as a
source of stem cell therapy. Embryonal stem cells, derived from the
human embryo is a more versatile type of stem cell, and amidst ethical
problems and technical problems regarding the delay in culturing a cell
line, is another source of stem cell, which is being sought for, in stem
cell therapy. The use of cord blood and human embryos for this therapy
brings the gynaecologists into focus as potential helpers in providing
these sources of stem cells.
What are stem
Stem cells are special
types of cells having remarkable ability for self-renewal and they remain
undifferentiated for indefinite periods of time, remaining as “reserve”
cells in the body.
Types of cells in
are considered the "master" cells of the body because they contain all the
genetic information needed to create all the cells of the body plus the
placenta. Human cells have this capacity only during the first few
divisions of a fertilized egg. After 3 - 4 divisions of totipotent cells,
there follows a series of stages in which the cells become increasingly
Pleuri potent cells
are a result of the next stage of division. These are highly versatile
and can give rise to any cell type except the cells of the placenta.
are at the next stage, meaning they can give rise to several other cell
types, but those types are limited in number. An example of multipotent
cells is hematopoietic cells—blood stem cells that can develop into
several types of blood cells, but cannot develop into brain cells. At the
end of the long chain of cell divisions that make up the embryo are
"terminally differentiated" cells—cells that are considered to be
permanently committed to a specific function.
Difference of stem
cells from other cells in the body:
The other types of
cells in the body are adult somatic cells, germ cells and embryonic
cells. The difference between adult somatic cells and stem cells is that,
adult somatic cells, once differentiated, cannot change their
speciality,e.g., adult liver cell cannot perform the function of an adult
pancreatic cell. Stem cells divide but do not differentiate or specialize
unless directed to do so under specialized environments either “in-vivo”
or “in vitro”.
Types of stem
cells: Two types of stem cells
have been identified.
somatic stem cells, which
can be unipotent or multipotent.
are those, which are capable of repairing or regenerating the tissues or
organ in which they exist.
Multipotent stem cells
are those that can differentiate into cells within the same family. For
e.g., Haemopoetic stem cells can form all blood cells like RBC, WBC,
Platelets, but not liver cell. Haemopoetic stem cells, bone marrow,
mesenchymal stem cells, neural stem cells, skin stem cells, etc are
examples of adult somatic stem cells.
stem cells, which are
Uses of stem cells:
Stem cells are being
tried in a variety of conditions. Many of the indications for which they
have been used have undergone controlled studies and many others are still
under investigations as conditions, which possibly could benefit from stem
cell therapy. Stem cell research is coming up in a big way in India and
quite a few workers have started using stem cells for a variety of
indications. Long-term effects of these therapies are yet to be
Since the 1980s, human
cells have been isolated from bone marrow
and used to treat patients with various hematologic malignancies. Bone
marrow transplantation also has been used successfully to treat immune
deficiencies, hemoglobinopathies, and metabolic diseases. Hospitals in
India treating Bone Marrow Transplants are; Manipal Hospital (Bangalore),
Apollo Hospitals (Chennai) and Indraprastha Apollo Hospital (New Delhi).
Myocardial infarction and other
cells are delivered to the heart through
an intracoronary catheter. Once the stem
cells have reached areas of infarcted
myocardium, they may improve contractility by differentiating into
functional cardiac myocytes and improve perfusion by releasing cytokines
that induce angiogenesis. The results have been positive in certain
trials and without effect in others. In some patients, newly developed
zones of myocardium have developed intrinsic electrical activity that
spurred malignant ventricular arrhythmias, requiring placement of an
implantable cardioverter defibrillator.
In India work in this area was
pioneered at All India Institute of Medical sciences, Delhi. Many
patients with this conditions are being given stem cell therapy in Asian
Heart Institute & Research Centre, NiCRM,
Nizam's Institute of Medical
Sciences (NIMS) , Frontier Lifeline Hospital, Chennai, Tirupati-based C
Venkateswarlu Institute for SCT, & Manipal Education and Medical Group's
(MEMG). Phase I multi-centric clinical trial using bone marrow
mononuclear cells on acute myocardial infarction are going on at five
hospitals in the country, that is, CMC; Sanjay Gandhi Post Graduate
Institute for Medical Sciences (SGPGIMS), Lucknow; Post Graduate Institute
of Medical Education & Research (PGIMER), Chandigarh; Research & Referral
Hospital, New Delhi; Air Force Medical College (AFMC), Pune and All India
Institute of Medical Sciences (AIIMS), New Delhi.
Alzheimer’s disease, Parkinson’s disease,
Multiple sclerosis, Spinal injuries:
Animal studies have found stem cells useful
in neurological diseases. Adult stem cells from bone marrow or adult
tissues, without viral contamination could be used for this. If embryonal
tissues are used, it should be less than 14 days old prior to formation of
neural tissue. Stem cell therapy for paraplegics following spinal injury
is being done at Global hospital, hyderabad as an ICMR project. . The
pilot study on acute ischemic stroke has also been initiated at AIIMS.
Reliance Life Sciences, Mumbai has characterised 10 stem cell lines,
including two neuronal cell lines, dopamine producing neurons and neurons
for patients of stroke.
Disorders of the eye:
In one of the programmes at L V Prasad Eye Institute (LVPEI), Hyderabad,
limbal stem cells are being used to repair the cornea surface.
Fanconi’s anaemia and some metabolic disorders have successfully been
treated using cord blood stem cells. Cord blood is more readily accepted
for paediatric cases as compared to adult patients. This is because,
children have a smaller physical size and the stem cell dose will be
smaller and easily available from the cord units even if the number of
stem cells present in them are limited.
stem cell therapy holds promise for many other conditions like type-1
diabetes, burns,and research is being done on stemcells to produce
sperms, obviating the need for sperm banks.
Sources of stem cells:
Adult stem cells
are present in the bone marrow and circulating blood. These cells are
readily accessible. Other rare, hard to identify AS cells are scattered
throughout the body. Stem cells from bone marrow take 3 weeks to
Cord blood stem cells:
Normally, cord blood is collected before the placenta is delivered. A
baby's umbilical cord blood, which is otherwise discarded, is a rich
source of stem cells endowed with the ability to regenerate and replace a
variety of tissues. In recent years, the concept of cord banking is
catching on in India. Interestingly, banking cord blood in a cord blood
bank is considered a "biological insurance" since the child from whose
umbilical cord the blood is collected can ostensibly stand to benefit from
it at any stage of his life. We however do not have enough cord blood
banks that have stored blood for more than 20 years or so and so it
remains to be seen if such blood can be used life-long. We have to see
whether cell lines can be maintained so long keeping their inherent
capacity to function as stem cells intact.
There are blood banks which offer to
store baby's cord blood in liquid nitrogen for a period 21 years for a fee
of around Rs.60, 000. The Chennai-based Cryocell has set up facilities to
preserve cord blood. Similarly, Life cell, yet another private stem cell
bank in Chennai says that about 1,000 expectant parents have enrolled to
bank the cord blood stem cells. The recently-set up Bangalore-based
Cryostem Karnataka Pvt Ltd is a cord blood stem cell bank as well as
research centre. The other cord blood banks in
Reliance life sciences, Mumbai,and Asia life cell Pvt Ltd, Chennai,.
The Cord Blood Stem Cells (CBSC) is derived
from the umbilical cord of consenting mothers. Cord blood is collected
from the part of the cord attached to the placenta after the baby has been
separated. The blood is collected in bags resembling blood collection
bags. It can then be sent to appropriate centers after labeling.
The pure stem cells are then separated from
the rest of the cord blood with a patented technology, and are
cryogenically frozen in vials, under strict laboratory conditions. These
Cord Blood Stem Cells are pure, with no red or white cells. This negates
the need for blood typing or HLA matching, safe,
with no graft versus host or rejection issues (as is the potential from
whole cord blood). Pluripotent, CBSC have been proven to regenerate every
single cell in the human body. (C. Verfaillie,
Univ. of Minnisotta July
In most cases, Cord Blood
Stem Cells Therapy involves one simple IV (intravenous) injection. Once
in the body, the cells migrate to the site of disease and begin replacing
damaged or missing cells. This process of noticeable reconstitution
usually peaks between 3 and 6 months following treatment. Often
significant results are noted at the one-month mark.
blood is a reasonable graft source for
adults who cannot find an HLA match in a bone-marrow registry or who need
transplantation sooner than the 3–4 months needed to obtain unrelated
adult-donor bone marrow.
Embryonal stem cells (ESC):
Embryonal stem cells are pleuripotent.
can be taken from the inner cell mass(ICM) of the blastocyst around days
5–6 after fertilization in mouse and days 8–9 in humans, isolated and put
in culture. The trophectoderm is removed and the inner cell mass (ICM) is
plated on to a feeder layer of mouse or human embryonic fibroblasts, which
is essential for the survival of the ICM. The ICM then flattens into a
compact colony of ESCs, which is than mechanically dissociated and
re-plated several times to give rise to stable cell line. When cultured in
the laboratory, human ESCs grow as compact colonies and usually require
the presence of feeder cells for their survival. When undifferentiated
human ESC colonies are detached from the feeder layer and transferred into
serum containing medium, they form multi-cellular aggregates called
embryoid bodies (EB) which can contain cell types representing all three
germ layers of the body: endoderm, mesoderm, and ectoderm.
Human ova are
denuded of their neucleus and the neucleus from a patient’s cell is
transferred in to the ovum. It develops into an embryo and the inner cell
mass is taken from its blastocyst and stem cells cultured from it. This
method has the advantage of using the patient’s own cells with no
potential of immune rejection and the stem cell being genetically
identical to cell source. People who believe that life starts before
conception are against the idea of growing human embryos and destroying
them, because human embryos according to them could be potential human
Culturing human embryonal stem cells can take up to 6 months and it may
be too long a period for critically ill persons who are looking up to stem
cell therapy as a last resort therapy.
Stem cell therapy
and the gynaecologist
especially in charge of IVF centres could be approached for embryos or
ova, which could be cloned to form embryos, which are a source of
pleuripotent stem cells. Obstetricians could be approached by cord blood
banks to make people more aware of the advantages of storing their baby’s
cord blood, which could be used any time in the next 20 or so years,
should the baby face the contingency of suffering from any haematologic/metabolic
condition requiring stem cell therapy during that time. Women with
history of relatives suffering from such conditions could approach the
obstetrician with a request to store the cord blood of her baby.
Stem cell nuclear
transplant or cloning of ova is still controversial as many people find it
repulsive to manipulate potential human beings for research even if they
are in the embryonic form. Culturing embryonal cells take a long time and
till this period is shortened, using embryonal cells to form useful stem
cells for therapy should be considered a research project as far as humans
are concerned. Animal studies have been encouraging.
blood is very costly and is at present feasible only for affluent
families. Whether the cell lines can be maintained for a long time and
whether any patient could benefit from it after 20 years is yet to be
seen. Except for haematologic/metabolic syndromes, at present, the baby
whose cord blood is being stored can have no other use for it as research
stands today. Use in juvenile diabetes is another potential use, but as
of now, it is still futuristic.
Cord blood of the
baby could be used for many conditions like cardiac conditions, neurologic
conditions etc of close relatives/acquaintances if the parents desire to
donate it for such purposes.
Storing cord blood is today being done with finances provided by the
mother delivering the baby. Thus it is difficult for an obstetrician to
be highly proactive and ask all patients to store their baby’s cord
blood. However, the media being very active about propagating information
about the uses of cord blood, every obstetrician should know the centres
with cord blood banks and the method of collecting, storing and
dispatching cord blood to such centres.