1. Basic Understanding of Stem Cell
Stem cells are the biological cells found in all multicellular organisms that can divide (through
mitosis) and differentiate into diverse specialized cell types and can self-renew to produce more
stem cells.
Properties of Stem Cell
 Self-renewal: It is the ability to go through numerous cycles of cell division while
maintaining the undifferentiated stage.
 Potency: It is the capacity to differentiate into specialized cell types. It requires stem cells to
be either totipotent or pluripotent—to be able to give rise to any mature cell type, although
multipotent or unipotent progenitor cells are sometimes referred to as stem cells.
Potency specifies the differentiation potential (the potential to differentiate into different cell types)
of the stem cell
Totipotent- stem cells can differentiate into embryonic and extra embryonic cell types. Such cells
can construct a complete, viable organism. These cells are produced from the fusion of an egg and
sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.
Pluripotent stem cells are the descendants of totipotent cells and can differentiate into nearly all
cells, i.e.cells derived from any of the three germ layers.
Multipotent stem cells can differentiate into a number of cells, but only those of a closely related
family of cells.
Oligopotent stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem
cells.
Unipotent cells can produce only one cell type, their own, but have the property of self-renewal,
which distinguishes them from non-stem cells (e.g., muscle stem cells).

2. Different types of Stem Cells
Embryonic Stem cells
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the
inner cell mass (ICM) of a blastocyst or earlier morula stage embryos. A blastocyst is an early stage
embryo—approximately four to five days old in humans and consisting of 50–150 cells. ES cells are
pluripotent and give rise during development to all derivatives of the three primary germ layers:
ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200
cell types of the adult body when given sufficient and necessary stimulation for a specific cell type.
They do not contribute to the extra-embryonic membranes or the placenta. The endoderm is composed
of the entire gut tube and the lungs, the ectoderm gives rise to the nervous system and skin, and the
mesoderm gives rise to muscle, bone, blood in essence, everything else that connects the endoderm to
the ectoderm.
Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic
stem cells (hES). Both have the essential stem cell characteristics, yet they require very different
environments in order to maintain an undifferentiated state.

3. Cord Blood Stem Cells/ Adult Stem Cells
Umbilical cord blood is blood that remains in the placenta and in the attached umbilical cord after
childbirth. Cord blood is collected because it contains stem cells which can be used to treat
hematopoietic and genetic disorders.
Cord blood is obtained by syringing out the placenta through the umbilical cord at the time of
childbirth, after the cord has been detached from the newborn. Cord blood is collected because it
contains stem cells, including hematopoietic cells, which can be used to treat hematopoietic and genetic
disorders.
Advantages of Cord Blood Stem Cells:
 Cord blood is a rich, natural, controversy-free source of life-saving stem cells.
 Stem cell rejection is less when using Cord blood. Hence it is possible to use cord blood from
non-tissue matched donors or a third party.
 Cord blood is available within a short time of three weeks compared to 4 months of time for
bone marrow stem cells.
 Cord blood collection does not involve any surgery and is painless with no side effects.
 Contamination does not occur with Cord blood, whereas bone marrow is likely to be
contaminated with viruses such as Epstein-Barr or Cytomegalovirus.
 Cord blood stem cells are the “youngest” and most adaptable form of cells, and the body more
readily accepts the cells into its system.
 Cord blood stem cells are more resistant to infection, have fewer side effects after the transplant
and require fewer transplant drugs than bone marrow stem cells.

4. A Brief History of Umbilical Cord Blood
Cord blood banking has a history that spans about twenty-five years. To date, about 8,000 people have
benefited from medical therapies using stem cells of the umbilical cord blood. Today cord blood is used
in medical therapies similar to the way stem cells from bone marrow are used. With cord blood
banking, it is possible to use cord blood stem cells to re-populate a blood and immune system.
Stem cell transplants started in 1983 when the first proposal was made to use umbilical cord blood as
an alternative source of stem cells. The first successful cord blood transplant took place in 1988. This
transplant was conducted in Paris on a six year old boy who was suffering from a blood disorder,
Fanconi’s Anemia. Stem cells from umbilical cord blood made it possible to regenerate his blood and
immune cells in his body and thus cure him.
The option of private cord blood banking became available to the public in 1992 when the first private
cord blood bank was established. In 1993 the first cord blood transplant from a non-relative was
conducted at Duke University. 1996 saw the development of the first US FDA Investigational New
Drug for cord blood.
In 1997, as a result of cord blood banking technologies, it became possible to conduct a successful cord
blood transplant on a 46 year old man suffering from chronic myelogenous leukemia.
The world’s first umbilical cord blood transplant was performed in 2000 with pre-implantation genetic
testing for a perfect tissue match. A National Cord Blood Program was started in 2004. Illinois declared
the right for women to opt for free cord blood banking in the year 2004
1983: The concept of using umbilical cord blood as an alternative source of stem cells for transplant is
proposed.
1988: The first successful cord blood transplant to regenerate blood and immune cells is performed in
Paris on a 6-year-old boy suffering from Fanconi anemia, a blood disorder.
Family seeks help in China through cord blood stem cell transplant
1992: The New York Blood Center establishes the first public bank for umbilical cord blood through
funding provided by the National Institutes of Health.
1992: University of Arizona banks the world's first cord blood sample specifically stored for family
use.
1993: First unrelated cord blood transplant occurs at Duke University.
1995: The first family bank, Cord Blood Registry, opens.
1996: The FDA launches an investigational new drug for cord blood under the National Institutes of
Health and National Heart Lung and Blood Institute-sponsored Cord Blood Transplantation Study.
1997: A successful cord blood transplant is performed on a 46-year-old man with chronic myelogenous
leukemia, a type of cancer, during a clinical trial using cord blood that was expanded "ex vivo," which
means outside of a living organism.
1998: The American Association of Blood Banks accredits the first family bank, Cord Blood Registry.
1998: Doctors conduct the first successful transplant to cure sickle cell anemia. Twelve-year-old Keone
Penn, suffering from sickle cell anemia, was treated at the Emory University Department of Pediatrics.
According to the National Cord Blood Program, one year after the transplant, doctors pronounced him
cured.

5. 2000: The world's first umbilical cord blood transplant is performed using pre-implantation genetic
testing to ensure a perfect tissue match. The transplant took place at the University of Minnesota
Medical Center-Fairview Blood and Marrow Transplant Services in Minneapolis.
2004: The Health and Human Services Appropriations Act for fiscal year 2004 provides funds to create
a National Cord Blood Program.
2004: The Institute of Medicine begins year-long study to make recommendations for a national cord
blood program.
2004: Illinois becomes first state to enact legislation mandating that birthing women have the option to
donate their babies cord blood to a public bank at no cost.
2005: The Institute of Medicine publishes a cord blood study, which includes a recommendation that
women must be provided with a balanced perspective on their cord blood option.
2005: U.S. Congress passes national cord blood legislation, The Stem Cell Research and Therapeutic
Act of 2005 (H.R. 2520), to create a national inventory of 150,000 high-quality cord blood samples.
2005: United Kingdom researchers discover embryonic-like stem cells in cord blood.
2005: More than 6,000 cord blood stem cell transplants have been performed worldwide.
2006: More than 8,000 cord blood stem cell transplants have been performed worldwide.
2007: President Bush issues an executive order directing research efforts to focus on alternatives to
pluripotent stem cells found in embryos. Umbilical cord blood stem cells are among the alternatives.
2008: More than 12,000 cord blood stem cell transplants have been performed worldwide

6. Cord Blood Harvesting
Umbilical cord blood is the blood left over in the placenta and in the umbilical cord after the birth of
the baby. The cord blood contains stem cells, including hematopoietic cells. Umbilical cord blood is
well-recognized to be useful for treating hematopoietic and genetic disorders.
There are several methods for collecting cord blood. The method most commonly used in clinical
practice is the “closed technique”, which is similar to standard blood collection techniques. With this
method, the technician cannulates the vein of the severed umbilical cord using a needle that is
connected to a blood bag, and cord blood flows through the needle into the bag. On average, the closed
technique enables collection of about 75 ml of cord blood.
Collected cord blood is cryopreserved and then stored in a cord blood bank for future transplantation

7. Umbilical Cord Tissue
Expectant parents can now also collect and preserve stem cells from the tissue of the umbilical cord,
whose medical name is Wharton’s Jelly. Whereas cord blood is a rich source of Hematopoietic stem
cells (HSC) that differentiate to form the lineage of blood cells, cord tissue is a rich source of
Mesenchymal stem cells (MSC). The International Society of Cellular Therapy (ISCT), has established
criteria for defining MSC. Mesenchymal stem cells differentiate to build bone, cartilage and connective
tissue, and they are also very effective at mediating the body’s inflammatory response to damaged or
injured cells. Harvesting the tissue of the umbilical cord can yield between 21 and 500 million MSC.
By comparison, a typical cord blood collection in a private bank has a median total nucleated cell count
of 470 million. For parents, private storage at birth of stem cells from both cord blood and cord tissue
offer more options for future medical use.
Numerous clinical trials are using MSC derived from the bone marrow of adult volunteers to treat heart
disease, stroke, bone disease and injury, and autoimmune diseases such as Type 1 Diabetes, Multiple
Sclerosis, and Crohn’s Disease. As yet, there are no clinical trials in humans using MSCs derived from
cord tissue. However, over 50 studies have used MSC derived from cord tissue to treat animal models
of human diseases, including: Lung Cancer, Parkinson's disease, Rheumatoid Arthritis, Sports injuries
to cartilage, and Type 1 Diabetes.

8. Difference between Cord Blood and Bone Marrow Stem cells:
Bone Marrow Stem cells Cord Blood Stem cells
 Invasive Procedure  Non- Invasive Procedure
 Painful  Painless
 100% sample matching is required. 6/6
match is required.
 3/6, 4/6 match is sufficient
 Donor is required.  Donor is required.
 Difficult to store and is not readily
available.
 Easy to harvest & store and is readily
available.
 Adult Stem Cells  Naïve fresh cells.
HLA matching
Whenever any type of transplantation is carried out, organ transplants or blood transfusions, it is
necessary to “match” markers that are known as antigens of the donor and the recipients. What are
these antigens? They are proteinaceous ‘tags’ or molecules that are present on surfaces of cells and
tissue of our body. These tags define our uniqueness. The moment a foreign ‘tag’ enters our system; our
body senses it and we mount an immunological response to the same. This is known as rejection. So if
a person undergoing a kidney transplant for example, receives a kidney whose tissue has antigenic tags
that are very different from those of his own kidney, his body will attack the transplanted kidney and he
will have what is known as a Graft Rejection. Similar is the case with blood transfusion and hence only
after determining the relevant blood group can the transfusion be successfully accomplished. Rejection
reactions are extremely strong reactions and can be fatal. Thus, the advantages of not requiring a
complete antigenic match while using cord blood for cure become evident. In a cord blood transfer, the
antigens that are matched are known as HLA (Human Lymphocyte Antigens); the same ones that are
matched during organ transplants. Now there are a large number of different HLAs found in our tissues
so not all of them are matched for reasons of practicality. Out of all of these, 6 important antigenic
clusters that are found to be of prime importance in rejection processes have been identified. These
major groups are, HLA A, B and DRB1. Complete matches between the donor and the recipient would
mean 2 pairs each of HLA A,B and DRB1; a total of six. This complete match is known as a 6/6 match
or a 6/6 HLA match. Sometimes an additional set of antigens are used for better matching. These are,
HLA C and DQ. Thus, complete matching of these additional markers yield a total of 10 points. So, one
may have a 6/10 match or a 10/10 match or a 5/10 match. Generally, the first 3 antigens are used and a
6/6 match is considered perfect. While a 5/6 match works best, a large number of successful procedures
have been carried out using just a 3/6 match that is only 3 out of the stipulated 6 markers match! That is
incredible and it exponentially increases chances of success in finding a donor. Today almost 70
different genetic disorders can be treated using Cord Blood.

9. Applications of Cord Blood Stem Cells
The first cord blood (CB) transplant was performed in 1988 in a patient with Fanconi anemia by
E Gluckman. The donor was his HLA-identical sister who was known by pre-natal diagnosis to
be HLA identical and not affected by the Fanconi mutation. The CB was collected and
cryopreserved at birth. The transplant was successful without GvHD and the patient is currently
alive and free of disease more than 15 years after transplant, with full hematologic and
immunologic donor reconstitution.
Diseases Treated
Stem cell transplants have been used since the 1960’s to treat a variety of diseases. In 1988 cord blood
stem cells were used for the first time in hematopoietic (blood) stem cell transplantation. Umbilical
cord blood stem cells have now been used in more than 15,000 transplants, through 2009, worldwide as
a valuable alternative to traditional sources of hematopoietic stem cells. Utilizing the process of stem
cell banking, cord blood stem cells also show great promise for potential future applications including
treatment and repair of non-hematopoietic tissues, gene therapies, mini-transplants, among others.
Potential Future Applications
Alzheimer’s Disease
Cerebral Palsy
Cardiac Disease
Diabetes
Epidermolysis Bullosa (rare genetic skin disease)
Lupus
Multiple Sclerosis
Muscular Dystrophy
Parkinson’s Disease
Rheumatoid Arthritis
Spinal Cord Injury
Stroke
This list represents major categories of diseases treated with stem cells and is not exhaustive. For
instance, there are more than twenty (20) specific types of Non-Hodgkin’s Lymphoma and numerous
types of Chronic Lymphocytic Leukemia, to name just two among many other.
Physicians and researchers have begun to make progress evaluating the safety and efficacy of umbilical
cord blood stem cells for certain therapeutic uses beyond blood cancers and genetic diseases of the
blood. The use of cord blood stem cells in treating conditions such as brain injury and type 1 diabetes is
already being studied in humans, and earlier stage research is being conducted for treatments of stroke,
and hearing loss. However, apart from blood disorders, the use of cord blood for other diseases is not a
routine clinical modality and remains a major challenge for the stem cell community.

10. Stages in Pregnancy
The process of prenatal development occurs in three main stages. The first two weeks after conception
are known as the germinal stage; the third through the eighth week are known as the embryonic period;
and the time from the ninth week until birth is known as the fetal period.
The Germinal Stage
The germinal stage begins with conception, when the sperm and egg cell unite in one of the two
fallopian tubes. The fertilized egg, known as a zygote, then moves toward the uterus, a journey that can
take up to a week to complete. Cell division begins approximately 24 to 36 hours after conception.
Within just a few hours after conception, the singe-celled zygote begins making a journey down the
fallopian tube to the uterus where it will begin the process of cell division and growth. The zygote first
divides into two cells, then into four, eight, sixteen, and so on. Once the eight cell point has been
reached, the cells begin to differentiate and take on certain characteristics that will determine the type
of cells they will eventually become. As the cells multiply, they will also separate into two distinctive
masses: the outer cells will eventually become the placenta while the inner cells will form the embryo.

11. Cell division continues at a rapid rate and the cells then develop into what is known as a blastocyst. The
blastocyst is made up of three later:
1. The ectoderm (which will become the skin and nervous system)
2. The endoderm (which will become the digestive and respiratory systems)
3. The mesoderm (which will become the muscle and skeletal systems).
Finally, the blastocyst arrives at the uterus and attached to the uterine wall, a process known as
implantation.
Implantation occurs when the cells nestle into the uterine lining and rupture tiny blood vessels. The
connective web of blood vessels and membranes that forms between them will provide nourishment for
the developing being for the next nine months. Implantation is not always an automatic and sure-fire
process. Researcher’s estimate that approximately 58 percent of all natural conceptions never become
properly implanted in the uterus, which results in the new life ending before the mother is ever aware
she is pregnant.
When implantation is successful, hormonal changes halt a woman’s normal menstrual cycle and cause
a whole host of physical changes. For some women, activities they previously enjoyed such as smoking
and drinking alcohol or coffee may become less palatable, possibly part of nature’s way of protecting
the growing life inside her.
The Embryonic Stage
The mass of cells is now known as embryo. The beginning of the third week after conception marks the
start of the embryonic period, a time when the mass of cells becomes a distinct human being. The
embryo begins to divide into three layers each of which will become an important body system.
Approximately 22 days after conception, the neural tube forms. This tube will later develop into the
central nervous system including the spinal cord and brain.
Around the fourth week, the head begins to form quickly followed by the eyes, nose, ears, and mouth.
The cardiovascular system is where the earliest activity begins as the blood vessel that will become the
heart start to pulse. During the fifth week, buds that will form the arms and legs appear.
By the time the eight week of development has been reached, the embryo has all of the basic organs
and parts except those of the sex organs. It even has knees and elbows! At this point, the embryo
weight just one gram and is about one inch in length.
The Fetal Stage
Once cell differentiation is mostly complete, the embryo enters the next stage and becomes known as a
fetus. This period of develop begins during the ninth week and lasts until birth. The early body systems
and structures established in the embryonic stage continue to develop. The neural tube develops into
the brain and spinal cord and neurons form. Sex organs begin to appear during the third month of
gestation. The fetus continues to grow in both weight and length, although the majority of the physical
growth occurs in the later stages of pregnancy.
This stage of prenatal development lasts the longest and is marked by amazing change and growth.
During the third month of gestation, the sex organs begin to differentiate and by the end of the month
all parts of the body will be formed. At this point, the fetus weight around three ounces.The end of the
third month also marks the end of the first trimester of pregnancy. During the second trimester, or

12. months four through six, the heartbeat grows stronger and other body systems become further
developed. Fingernails, hair, eyelashes and toenails form. Perhaps most noticeably, the fetus increases
quite dramatically in size, increasing about six times in size. The brain and central nervous system also
become responsive during the second trimester. Around 28 weeks, the brain starts to mature much
faster with activity that greatly resembles that of a sleeping newborn.
During period from seven months until birth, the fetus continues to develop, put on weight, and prepare
for life outside the womb. The lungs begin to expand and contract, preparing the muscles for breathing.
While prenatal development usually follows this normal pattern, there are times when problems or
deviations occur.
Basic Questions:
1. What are Stem cells?
Stem cells are the master cells found in all multicellular organisms that can divide and differentiate into
diverse specialized cell types and can self-renew to produce more stem cells.
2. What are the different kinds of stem cells?
In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the
inner cell mass of blastocysts, and adult stem cells, which are found in various tissues.
3. What are adult stem cells?
Adult stem cells are undifferentiated cells, found throughout the body after embryonic development
that multiply by cell division to replenish dying cells and regenerate damaged tissues.
4. What are the different sources of adult Stem cells?
The different sources of adult stem cells: Bone Marrow, Cord blood, Adipose tissue, Dental pulp &
peripheral blood.
5. What is cord blood stem cell?
Cord blood is the blood remaining in the placenta and attached umbilical cord after childbirth – both
which are normally discarded. Significant research now shows that cord blood contains hematopoietic
stem cells which can be used in various blood related disorders. Cord blood is now considered one of
the most important stem cell sources.
6. Why it is necessary to go for cord blood stem cell preservation?
It is necessary to go for cord blood stem cell preservation as it is a once in a lifetime opportunity to
store your baby’s cord blood stem cell which can be done only at the time of delivery. It is a biological
cover not only for the child but for the entire family. Cord blood stem cells have been successfully used
in transplant medicine for more than 20 years. Cord blood has been used to treat many life-threatening
diseases including leukemia, other cancers, and blood disorders.

13. Cord blood is being researched now for use in regenerative medicine where stem cells may help induce
healing or regenerate cells to repair tissues. This exciting new area of medicine has led to clinical trials
using cord blood in experimental therapies to treat cerebral palsy, brain injury, and juvenile diabetes.
7. How is the collection process done?
Collecting cord blood is a simple, safe, and painless procedure that usually takes less than five minutes
and happens immediately after birth. After the umbilical cord has been cut, the remaining blood in the
cord is collected. The cord blood is then shipped to the laboratory and frozen in cryogenic storage
tanks for long term preservation.
8. How is cord blood stem cell preserved?
Cryopreservation is the method used for long term storage of cord blood stem cells. By reducing the
temperature of the cells, we effectively shut down all biochemical systems preventing any ageing of the
cells. It is preserved at -196 degree Celsius with the help of liquid nitrogen.
9. How long can the cord blood be preserved?
Cord blood stem cells can be preserved for a long time. According to the existing data, cord blood
hematopoietic stem cell has been safely preserved under cryopreservation for more than ten years. The
history of cord blood preservation is nearly twenty years till now.
10. Who all can use the baby’s cord blood stem cells?
The baby will always be a perfect match and may use his or her own stem cells for a number of
diseases. Any family member who is a suitable match may be able to use your baby's cord blood stem
cells.
11. What is HLA Matching?
HLA matching is the criteria used to determine donor and recipient compatibility and generally refers
to six proteins called human leukocyte antigens (HLA) that appear on the surface of white blood cells
and other tissues in the body. A transplant can only be performed if there is an adequate HLA match
between donor and recipient. In case of cord blood stem cells, we don’t require a 100% match. A
transplant physician can perform a transplant even in 3/6 or 5/6 match.
12. What is graft versus host disease?
Graft-versus-host disease (GVHD) is a common complication after a stem cell transplant or bone
marrow transplant from another person (an allogeneic transplant). Immune cells (white blood cells) in
the donated marrow or stem cells (the graft) recognize the recipient (the host) as "foreign". The
transplanted immune cells then attack the host's body cells. Baby’s banked cord blood stem cells can
help reduce GvHD because the immune cells within the cord blood are less reactive than the immune
cells in bone marrow or peripheral blood.

14. 13. How are cord blood stem cells different from other stem cells?
•There is less risk of complications when used in transplants.
•They are immediately available, and early treatment can minimize disease progression.
•Collection of cord blood is simple, safe, and painless.
14. What is cord Tissue?
Umbilical cord tissue could be a source of plentiful stem cell called the mesenchymal stem cells.
Mesenchymal stem cells are present in the umbilical cord's gelatinous material called Wharton's jelly .
These cells could be expanded to a greater number, remain remarkably stable and might not trigger
strong immune responses.