Umbilical cord blood stem cells

Text author: Assistant Professor Mirando Mrsić, M.D., D.Sc.
For the last ten years, scientists have paid more and more attention to research in the area of growth and development of stem cells. Research in this field, especially when we are talking about cloning and fetal cells, has been a topic of great controversy and many ethical disputes. As a result of the doubts raised at the beginning of the century, research has turned towards the study of umbilical cord blood stem cells.

1. What is umbilical cord blood?

Cord blood, which is also called placental blood, is the blood that remains in the umbilical cord and placenta following the birth and after the umbilical cord is cut. Until some 10 years ago, this blood was routinely discarded with the placenta and umbilical cord. Research has shown that umbilical cord blood is an extremely valuable source of stem cells which can produce bone marrow cells and other cells.

2. What are stem cells and how are they used?

Stem cells are the body's "master" cells because they create all other tissues, organs, and systems in the body. The stem cells found in cord blood are the building blocks of bone marrow cells and the immune system. These cells produce the erythrocytes, the cells that transport oxygen; leukocytes, the cells that defend the organism; and trombocytes, the cells which stop bleeding. There are three sources where these cells are commonly found: bone marrow, peripheral blood and umbilical cord blood.

Only recently has it been discovered that these cells have the ability to transform into other cells and organs. This discovery holds significant promise for improving the treatment of some of the most common diseases such as myocardial infarction, spinal cord injuries, brain infarction and Alzheimer's disease.

Currently, stem cells are primarily used in the treatment of hematological illnesses such as leukemia and lymphoma. After chemotherapy, an infusion of stem cells is performed. The stem cells migrate to the patient's bone marrow where they multiply and regenerate all of the cells to create a new blood and immune system for the patient.

3. What is the principle of stem cell treatment?

Today's treatment principle is to use high doses of cytostatic and radiation to destroy the damaged bone marrow, but this also destroys the patient's stem cells. Without other stem cells, either one's own umbilical cord stem cells which have been stored in liquid nitrogen, donor stem cells or umbilical cord stem cells, the patient's survival is impossible. Without the help of these cells, the patient's life expectancy is no longer than 2-3 months. Medical research has shown that, besides bone marrow cells, stem cells can also produce muscle cells, nervous cells and blood vessel cells. As this field is currently the most intensely researched, some major breakthroughs are expected.

4. What types of diseases are treated with cord blood stem cell transplantation?

Every day more and more illnesses are being treated with umbilical cord stem cell transplantation:

Malignant illnesses:

  • Acute Lymphocytic Leukemia
  • Acute Myelocitic Leukemia
  • Chronic Myelocitic Leukemia*
  • Myelodysplastic Syndromes
  • Neuroblastoma

Non-malignant illnesses:

  • Adrenoleukodystrophy
  • Amegakaryocytosis Thrombocytopenia
  • Blackfan-Diamond Anemia
  • Dyskeratosis Congenita
  • Fanconi Anemia
  • Gunther's Disease
  • Hunter's Syndrome
  • Hurler's Syndrome
  • Aplastic Anemia (severe)
  • Kostmann Syndrome
  • Lesch-Nyhan Syndrome
  • Osteopetrosis
  • Severe Combined Immunodeficiency (SCID)
  • Thalassemia
  • X-Linked Lymphoproliferative Disorder

*If there is no result after Glivec treatment

5. Are cord blood stem cells different than other types of stem cells?

Yes. Umbilical cord stem cells are the youngest cells. Another source of stem cells, embryonic stem cells, has been at the heart of heated ethical debate. Currently, embryonic stem cells are not being used to treat humans. A third category of stem cells is adult stem cells, such as those found in bone marrow and peripheral blood of both children and adults. Adult stem cells serve very specialized roles and are not as proliferative as those found in cord blood and embryonic cells.

6. Why are cord stem cells attracting so much attention?

Easier to match
In cases of bone marrow stem cells transplantation or peripheral blood, there has to be a perfect match between the donor and recipient in order to avoid life threatening complications such as the recipient having an adverse reaction to the transplant. Cord blood cells, however, are less mature and have a smaller immunogenic potential than in bone marrow and can be successfully used even when there is only a half-match, or in some cases at least achieve a better result than with classic stem cell transplantation.

Immediate availability
Banking cord blood ensures that these stem cells can be immediately available if they are needed for treatment. Early treatment of many illnesses can minimize disease progression. The sooner the treatment begins, the greater the chances are of a successful transplant. Because of this reason, cord blood has an advantage over other sources of stem cells.

Less frequent complications
Since cord blood stem cells are less immunogenic, and not yet mature, adverse reactions to the transplant are not as frequent. According to research, the frequency of an adverse reaction in patients treated with cord blood is around 6% and the frequency in patients treated with bone marrow and peripheral blood is 15-20%.

7. What is an adverse reaction to the transplant (Graft versus Host Disease)?

An adverse reaction to a transplant is frequent and in some cases lethal. Reactions occur when the stem cells do not recognize the patient's body (the host) and attack it. The same reaction occurs with organ rejections. The difference is that with organ rejection the body tries to reject the transplanted organ, and here the transplanted cells reject the host. This is one reason your donor's HLA antigens need to match yours as closely as possible.

8. What is the HLA system?
Human leukocyte antigen (HLA) system differentiates self cells and non-self cells (cancer cells, bacteria, viruses, etc.). These antigens reside on the surface of leukocytes and other cells in the body. They are divided into 6 subgroups that are classified by alphabetical letters. In classic transplantation, compatibility has to be 6/6, that is all 6 subgroups have to match. In the case of umbilical cord blood transplantation, compatibility has to be 3/6, that is 3 subgroups have to match. The reason being is that umbilical cord stem cells aren't mature enough and after transplantation they don't cause a strong reaction like adult bone marrow stem cells.
9. How is cord blood collected?

Collecting cord blood is a simple procedure. After the umbilical cord is clamped off from the newborn, a wide syringe is inserted into the umbilical vein and the blood is collected by gravity drainage yielding 50-110 mL of cord blood. Until a few years ago that blood was routinely discarded. Since 1995, cord blood has systematically been collected and used in the treatment of many diseases in many countries.

10. Is the amount of cord blood collected important?

YES, it is important to collect every milliliter of cord blood. The number of stem cells is in proportion to the amount of cord blood. In many cases, the number of stem cells correlates with the saved volume. The bigger the volume, the more cells there are. That is especially important in the case when cord blood is donated for the benefit of the general public. In the case when cord blood is saved for private purposes, volume is also important, but not essential for successful treatment, because the cord blood is stored for the exclusive use of the donor.

11. How prevalent is collecting cord blood in Croatia?

The cord blood bank was established on March 28, 2007, and the first cord blood was stored in the voluntary blood bank on July 5th. For now, only the major maternity clinics in Zagreb are equipped for collecting cord blood, namely, the Petrova Clinic for Obstetrics and Gynecology and the maternity ward at Clinical Hospital Merkur. Due to the great efforts of the Ana Rukavina Foundation, all the maternity hospitals in Croatia should offer that option by next year.

12. Is there any risk to the child or mother during the collection of cord blood?

NO. The cord blood is collected after the baby has been born and the umbilical cord has been clamped and cut. The collection is painless, easy and safe for the mother and baby. Collecting cord blood will not alter the normal birthing process in any way. In most cases, collecting the cord blood only lasts about 5 minutes because coagulation of the blood in the umbilical cord and placenta begins after that.

13. Is it necessary to have special materials for collecting cord blood?

NO. The materials for the voluntary cord blood bank are donated by the Ana Rukavina Foundation and the family doesn't have any expenses to bear. When cord blood is collected for private purposes, the materials are provided by the institution in which the procedure is to be done. In that case, the cost of the materials is included in the price of collecting and storing the cord blood.

14. What are the possibilities of cord blood storage in Croatia?

Around the world, as well as in Croatia, there are two types of cord blood banks: public and private. The latter are cord blood banks for the exclusive use of the donor. In some countries, they are two separate institutions, while in other countries they operate under the same roof. The regulations regarding public and private cord blood banking in Croatia have been passed by the Ministry of Health and Social Care. They stipulate that the private cord blood bank cannot be more than 30% of the total banking capacity. Currently, the voluntary bank is operational and we anticipate that by the end of the year the private cord blood bank will be in function. The bank will be located at the Institute for Clinical Transfusions in the Clinical Institute for Laboratory Diagnostics KBC Rebro Hospital, Zagreb, Kišpatićeva 12. For more information, please call...

15. Why do we store the cord blood?

Tens of thousands of families in the world have chosen to save cord blood, whether for private purposes or in voluntary banks. Cord blood stored in voluntary banks is part of the large Cord Blood Registry. The CBR contains all the information about the stored cord blood so that the right type of cord blood can be easily found for transplantation. The private bank, that is the cord blood bank for one's own family's use, isn't included in this Registry because it is not intended to be used in the treatment of patients, rather for the exclusive use of the donor or donor's relatives.

Storing cord blood is a once-in-a-lifetime opportunity - only at birth.

16. How long can cord blood be stored?

In public cord blood banks, the cord blood can be stored for an unlimited period of time, that is, until the moment someone needs it. In the situation that the cord blood is needed by the donor, and it had not been used by someone else, the cord blood is given free of charge. In the case that the cord blood is transplanted into someone other than the donor, a fee is charged and it includes the costs of collecting, processing, storing and transportation. The current cost of a transplantation is around 15-20,000 Euro and is covered by the insurance company. According to the available information, the cost of collecting, processing and storing the cord blood in private banks is around 1,500-2,000 Euro. The annual maintenance fee is charged for a period of 18 years, until the newborn donor reaches adulthood. At that time the donor can choose to continue storing the cord blood or donate it to the public bank. The difference between the price of the public bank and the private bank is the cost of collecting, processing, and storing the blood for such a large number of specimens which may never be used. The chances that cord blood will be used for transplantation are 1:30,000 -100,000, depending on ethnicity. Since it is not known which blood will be used, all the collected blood must be processed, tested and stored in the same way.

17. If I decide to store cord blood in a private bank, can I use it for other family members?

Cord blood that is stored in a private bank belongs to the family and can be used in the treatment of any family member. If you have more than one child, it is highly recommended to save the cord blood of each child, the reason being is that cord blood is less immunogenic and therefore a better source of stem cells.

18. Can all cord blood be stored in banks?

No, unfortunately. As we are talking about transplantations, the blood must satisfy the strict criteria for the number of stored cells, sterility and the absence of infectious diseases. Based on the experience of other banks, only one out of every three donations of cord blood meets all the criteria for storage. In the private blood bank, the only requirement is an adequate number of cells. Aside from sterility the other criteria are not crucial. In this case, HLA tissue typing or testing for viruses are not done. In cases when there is a small volume or number of cells, the family decides whether the blood will be stored or not.

19. Is collection of cord blood different with a cesarean section?

Having a cesarean section does not change the process of collecting cord blood.

20. How is the cord blood transported to the bank?

Cord blood can be kept at room temperature for up to 36 hours without having to be stored in a refrigerator. However, it is best to get the blood to the bank as soon as possible. Since cord blood is currently only collected from hospitals in Zagreb, the cord blood is transported to the bank at least once a day. It is foreseen that cord blood from hospitals outside of Zagreb will be shipped by a medical courier.

21. How long do frozen cord blood cells remain viable?

For the time being, it is not known how long the collected cord blood cells can remain viable if stored in liquid nitrogen (at -196°C). Based on other research it can be assumed that they can be stored forever under controlled conditions.

The establishment of the cord blood banks

Establishing cord blood banks is a sign of technological advancement and puts Croatia in a position among countries where such programs have existed for a long time. The foundation of the bank in Zagreb will increase the availability of stem cells needed for transplantation.