Cord Blood_ Biological Insurance or Gimmick__ _ Davidson Institute of Science Education

12.3.2021 Cord Blood: Biological Insurance or Gimmick?
| Davidson Institute of Science Education
Cord Blood: Biological Insurance or Gimmick?
h Dr. Yochai Wolf

c September 17, 2016
m 15 min Leave room for doubt
Almost all maternity patients receive proposals to

preserve fetal cord blood for a great amount of money,
with the promise of the possibility to cure many diseases
in the future. Is all the hype true? What can be done with
cord blood and what are the disadvantages of the
treatment? Also – what are the public repercussions of
the method?
Young parents nowadays are faced with many issues arising from technological
developments and the availability of information on the Internet. Should they
vaccinate their children? Is it possible to give up breast-feeding? Should they buy
organic food? What about genetically modified food?
In recent years the new trend causing a dilemma is whether to preserve umbilical
cord blood for private use? Today cord blood is already being used to treat
dozens of blood diseases, such as primary immunodeficiency ("bubble children"),
blood cancers and certain types of anemia. Commercial companies now offer,
with often-aggressive advertising, paid preservation of cord blood for personal or
family use. Beyond available treatments, the companies promise frozen cord
blood will be used in the future to treat disorders such as autism and cerebral
palsy.
Like other medical issues, cord blood preservation is a complex subject and the
whole field is still evolving. This article will present the latest scientific findings and
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12.3.2021 Cord Blood: Biological Insurance or Gimmick? | Davidson Institute of Science Education
shed some light on how cord blood is currently being used in the field.
Cord blood is the blood collected at birth from the umbilical cord and placenta -
the tissues that feed the fetus and connect it to its mother. Cord blood has been a
focus for the last thirty years of research because it is rich in stem cells, which can
develop into a wide variety of cells throughout the body. Cord blood is rich mainly
in Hematopoietic stem cells that develop into the different blood cells, which
are vital for treating various blood diseases. Many of these diseases are treated
with bone marrow transplants because bone marrow contains these blood-
forming stem cells that are capable of replacing the defective stem cells of the
patient.
In order to successfully transplant blood-forming stem cells one requires a match

between a donor and recipient. The mismatched recipient may reject the implant
or the implant itself might attack the recipient's body - as so often happens when
transplanting bone marrow in blood cancer patients.
Blood engraftment depends on “matching” genes known as HLA, which mark the
differences between the body's own cells and foreign cells. Each person has six
copies of these genes, and in order to be able to conduct a successful transplant a
maximal match is required between all six copies of the donor and the transplant
patient – a statistically rare combination. Without a match, the T cells of the
immune system will recognize the graft or the body of the recipient as foreign
and attack it. If the implant matches only four or five copies of HLA, its
engraftment can be problematic.
A fight against the numbers

The great advantage of cord blood over bone marrow transplantation lies in the
fact that it produces a weaker rejection response. Cord blood T cells are younger
and less "experienced" and therefore more "promiscuous" than those of adult
bone marrow so their attack on the "alien" body is gentler. When a matching HLA
donor cannot be found even among the patient’s relatives, the dose can be
transplanted from cord blood; the engraftment will be "milder" than when
matched with a less than optimal donor.
Another advantage of cord blood is that it contains not only the blood-forming
stem cells, but also Mesanchymal stem cells, which develop into cells that are
not within the blood system such as bone, fat, heart and cartilage cells. But as we
shall see, successful results are not yet prevalent.
A significant disadvantage of cord blood cells is the tiny amount that exists
compared to that in a bone marrow dose. Researchers estimate that a single dose
of cord blood that contains approximately 900 million cells can be used to treat
children, whereas adults probably need several doses. Today, attempts are being
made to increase the number of blood-forming stem cells within cord blood, so
that one dose will be enough even for an adult. For example, the company
Gamida Cell recently announced it has developed a breakthrough product for
this purpose, but it is still currently under development.
Other disadvantages of cord blood are its prolonged engraftment and

recovery time compared to a bone marrow transplant; the recipient remains
in a state of immune deficiency and is vulnerable to infection for a longer period.
A brief history
"Cord blood transplants account for about five to ten percent of the world's stem
cell transplants. Israel performs about 10-15 such transplants per year", says
Professor Isaac Yaniv, Head of Hematology-Oncology at Schneider Children’s
Hospital. "When a patient needs a transplant as part of treatment for a blood
disease, cord blood is the third priority because of the slow recovery and we have
much more experience with bone marrow transplantation.
"First of all we are looking for a donation from a sibling, because there is a twenty-
five percent chance to have a full HLA match. If there are no matches or no
siblings, we look on our bone marrow donor database or for an ordinary blood
donation (i.e. peripheral blood), while at the same time we also look for a cord
blood donation. Whenever it comes to diseases of blood, cord blood becomes a
very effective resource due to high availability of public databases. Sometimes
there is not enough time to find a suitable bone marrow donor, and because a
cord blood match is less stringent, it is preferable".
The idea of using cord blood to treat diseases was first conceived by Professor
Hal Broxmeyer in the early 1980s. The first cord blood transplant was done in
France in 1988 on an American boy who suffered from Fanconi anemia. His
mother had just given birth to a baby girl who had a complete HLA match to the
sick child, and the new sister was not a carrier of the disease. Due to the urgency
of the transplant and the inability to take the new baby’s bone marrow,
Broxmeyer took the baby's cord blood and flew to Paris with the sick child and
the frozen cord blood. He also needed to buy a full priced plane ticket for a seat
for the cooler that held the specimen.
In France Prof. Eliane Gluckman completed the transplant. The first experiment of
its kind was successful and the recipient lives today as a healthy individual. Since
then there have been around thirty thousand transplants worldwide, with the
vast majority being foreign donors rather than family members. Over the last
three decades the results from using umbilical cord blood have greatly improved
thanks to a better selection of patients and cord blood samples, and the
proportion of patients who survive the transplant is constantly increasing.
Meanwhile in Israel
Prof. Arnon Nagler at the Sheba Medical Center did the first cord blood transplant
in Israel in 1994. The first transplantation using umbilical cord blood from a
private bank was only performed in 2011. In Israel there are two public banks
for umbilical cord blood, one managed by the MDA (Magen David Adom) and the
other by Bedomaich Chayi. There are also three private banks: Cryosave, Ta
Lachaim and the Taburit Bank of Sheba Medical Center, which also stores
samples for public use. The Ministry of Health shut down another private bank,
Biocard, in 2013, due to unmet regulations. Individuals that paid to have their
cord blood stored by this company on behalf of their descendants are still
looking for their stock.
Private or public
The question of whether to preserve cord blood in a private bank is complex and
multi-layered. One of the main reasons to store in a private bank is a chance to
carry out autologous transplants (using one’s own stem cells). But most blood
diseases, including blood cancers, are discovered in early childhood and are due
to a genetic defect, so cord blood cells will carry the defect and the implant will
not help the patient.
According to the most up-to-date scientific and medical knowledge, the chances
of being able to use one’s own cord blood for a transplant is very low. In 2008 a
committee for the American Society of Blood and Marrow Transplantation
estimated that the chances of such a transplant is between 1:2500 to 1:200,000
only. It is recommended to encourage cord blood for use within a family only if a
family member has a relevant blood disorder. However, according to other
estimates the chances for a successful transplant are considerably higher. An
article responded against the position of the American Society estimating that
the chance is actually 1:400 in adult patients. Although it is important to note
there are only very few reports in the literature on the use of autologous cord
blood in blood cancers.
Transplantation when not used on oneself has a twenty-five percent chance of

being a match for siblings. Therefore, young parents could ask themselves if they
want to invest in a particular insurance that is only useful for genetic blood
disease, and where the chance of success is about twenty-five percent.
"Childhood leukemia already develops while in the womb and so cord blood cells
also have leukemia", explains Prof. Yaniv. "It has happened quite a few times
where parents of a sick child with leukemia are pleased they have preserved cord
blood, and I have to explain to them that it cannot be used. The only situation in
which I would recommend a transplant for family use is in the case of a sick child
whose mother is pregnant. In this case we want to freeze the cord blood of the
sibling to see if they are a suitable donor. If so, this cord blood can be saved for
only two years. After this time we already prefer to use a sibling bone marrow
donor, thanks to a more rapid recovery from the procedure. Just this year, this
short-term preservation was added to the standard health insurance basket".
Private storage advocates argue that despite the low probability of self-transplant,
the stem cells will provide a tremendous therapeutic potential that is still
untapped, for example treating diseases such as cerebral palsy, diabetes,
autism and Parkinson's. According to these camps, private storages of cord
blood will be ready for regular use in the near future with significant health
benefits to those who prepared with such insurance.
Although it is quite possible, it is obvious that private banks raise these

arguments with aggressive marketing campaigns because they have an interest in
promoting the subject. Despite the encouraging experiments in these areas, and
despite cases in which autologous transplant of umbilical cord blood has
improved the condition of patients - for example in cerebral palsy (here, here
and here), these successes are still very rare and treatments are only at their first
steps. After all, who is going to show a YouTube video for a patient whose
situation has not improved, or even worsened following a transplant?
Treatments and knowledge are still at their first steps. Cord blood bank | Photo: Science Photo Library
"No one today can know if stem cells will be used to treat diseases that are not
blood disorders, such as autism," says Prof. Zvi Lapidot of the Immunology
Department at the Weizmann Institute of Science, an expert in hematopoietic
stem cells. "Blood-forming stem cells have a remarkable feature - once they are
injected into the blood they know to return to their niches in the bone marrow
and differentiate into various blood cells. Other stem cells do not know how to do
this and hence there lies the great difficulty in working with them to get good
results."
Prof. Lapidot stressed that despite progress in stem cell research, there is a long
way to go before their clinical use. "Human embryonic stem cells are able to
differentiate into any cell of the body, and this was discovered nearly twenty years
ago, and the technology to of creating stem cells from adult cells has existed
for ten years, but these developments have not saved even one person yet.
Perhaps in the future it will be possible, but we won’t see this any time soon. So
I’m not sure that anyone who preserves cord blood today for personal use, aside
for blood diseases, could benefit from it. This technology might evolve in a few
decades, if ever. The claim that in the future cord blood might possibly cure
autism, for example, is nothing but a commercial marketing ploy."
Currently the consensus of scientific-medical centers is that one is encouraged to

store cord blood in public banks, and not privately, with the rationalization that
family or personal use of such blood is very unlikely. This position is supported by
other organizations such as the American Society of Blood and Marrow
Transplantation, estimating that the chance to use cord blood stored at a public
bank is one hundred times greater than compared to a sample that is stored in a
private bank. The American Academy of Pediatrics, the American Congress of
Obstetricians and Gynecologists and the World Marrow Donor Association
also agree on this. There is a considerable difference between private banks that
present cord blood preservation as “biological insurance'', and the concept of
scientific-medical establishments that see cord blood as a "long term investment"
that might or might not justify itself in the future.
Quality control
Another issue is the "life span" and quality of cord blood throughout its
preservation. Studies have shown that stem cells from cord blood are still able to
generate blood cells and other cells from cord blood stored twenty years ago.
However, banks have only existed for a little more than two decades so nobody
knows what will be the quality of the sample after a longer period. It also depends
on the quality of the sample when it is actually taken.
International standards require that all cord blood samples contain at least 900
million nucleated cells, i.e., not including red blood cells. However, according to
one estimate, about ninety percent of the samples in public cord blood banks
around the world do not meet these criteria, so they are donated to science.
Theoretically, even private banks are committed to these international
standards, but studies have found that the amount of cells in cord blood stored
in private banks across the United States is much smaller than its public banks.
According to the Israeli practice of private banks, they are not committed to any
such threshold. "We know for sure of samples preserved in private banks that do
not contain the minimum amount necessary for a transplant," says Prof. Yaniv.
Most cord blood samples that do not meet the threshold conditions for
preservation in public banks are donated to science. However, samples kept in
private banks cannot be donated to science without the consent of the family,
even if they are unusable for transplantation. If all cord blood donors were
storing in private banks, research would come to a complete halt, even though
future use of cord blood depends entirely on this research.
Public interest
Another important aspect is the public’s responsibility for storage. Someone who
preserves the umbilical cord blood of their children for personal use is like a
person who wants to donate his organs after his death only for his family, and not
for the general public. This has many implications, such as the availability of cord
blood to ethnic minorities. Most bone marrow donors in the western world are
white, and therefore ethnic minorities find it harder to find a bone marrow
donor. The option to settle for only partially genetically matched cord blood
donations increases the chances for minorities to be able to receive donations.
This is especially true for a small yet diverse population like that of Israel. The
2009 report of the Bone Marrow Donors Worldwide organization showed that
forty-two percent of donations from public cord blood banks in Israel were
of unique tissue typing characteristics - evidence of the sectarian and ethnic
diversity in Israel. This is another reason to encourage public storage of cord
blood, ensuring availability of donations to the general public, including

minorities.
"The state should invest in the representation and participation of ethnic

minorities such as Arabs, Bedouins, Bukharis, Yemenites and Ethiopians – in both
cord blood banks and bone marrow banks," says Prof. Yaniv. "All of these
minorities have difficulty finding donors and there is no point in continuing to
collect donations of Ashkenazi Jews who are well represented in the storages.
Among the Arab population, for example, there is strong opposition to donation
to reservoirs, so public relations work needs to be done here."
A fundamental need
Perhaps from some of the aforementioned, a negative image has emerged
regarding private banks as allegedly misleading the public and selling
misconceptions, as expressed by former Health Ministry Director-General Dr.
Ronni Gamzu. Of course the truth is more complex, and these banks need to find
a real need to sell to the public. The amount of storage of cord blood in public
banks in Israel reaches several hundred packets a year. In 2011 such banks had
about 8,000 cord blood samples, and if we take into account that for many cases
two blood samples are required for transplantation, very few patients will be able
to benefit from the contribution.
For years, public banks were funded by donations. Only in 2007 the cord blood
bill, initiated by Knesset Member Moshe Kahlon, was passed, and only in 2010
was the law implemented, following lobbying by Knesset Member Zeev Bielski,
where public banks activity was allocated a budget of three million NIS a year.
As mentioned above, in Israel there is a fundamental need for a variety of

donations of umbilical cord blood because of the many ethnic minorities that are
not represented in the reservoirs, and therefore their difficulty in receiving
donations. Entering this vacuum are the private companies, together with parents
who fear that the state will not care for their children when necessary. This is a
life-saving channel that the country should invest more in, rather than shifting the
decision and the responsibility onto the parents themselves.

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12.3.2021 Cord Blood: Biological Insurance or Gimmick?

| Davidson Institute of Science Education

Cord Blood: Biological Insurance or Gimmick?

h Dr. Yochai Wolf

m 15 min Leave room for doubt

Almost all maternity patients receive proposals to

In order to successfully transplant blood-forming stem cells one requires a match

A fight against the numbers

Other disadvantages of cord blood are its prolonged engraftment and

Transplantation when not used on oneself has a twenty-five percent chance of

Although it is quite possible, it is obvious that private banks raise these

Currently the consensus of scientific-medical centers is that one is encouraged to

blood, ensuring availability of donations to the general public, including

"The state should invest in the representation and participation of ethnic

As mentioned above, in Israel there is a fundamental need for a variety of

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