Blood is a liquid, viscous, circulating tissue that moves through the veins of our body. It is composed of fluid plasma and blood elements (red cells, white cells and platelets). The main function of blood is to carry nutrients (oxygen, glucose, and microelements), amino acids, lipids and hormones to tissues and to remove waste components.

Blood elements:

• Red blood cells (erythrocytes – 96%). Their role is to transport oxygen from the lungs to tissues and remove the carbon dioxide from the tissues and carry it back to the lungs. The function of red cells is also to bind or release these molecules. The lifespan of red cells is around 120 days.
• White blood cells (leukocytes – 3%) are a part of the immune system and are engaged in defensive and metabolic processes of an organism.
• Platelets (thrombocytes – 1%) – are important for healthy growth of the vascular endothelium and participate in hemostasis (responsible for clotting or coagulation of blood).

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FORMATION OF BLOOD ELEMENTS

Mature blood elements have the ability to divide, and therefore they must be constantly renewed. Hemopoiesis (hematopoiesis) is a very complex process during which certain organs in the human body produce blood elements. These elements go through a division phase, a differentiation phase and a phase of maturation (See Pic.1). There are several theories about the origin of blood elements and a final exploration of these theories has not been completed yet.

Pic.1: (source: - http://cs.wikipedia.org/wiki/Krvetvorba

According to the differences in hematopoiesis and organs in which blood elements are produced, in general, we divide hematopoiesis into two essential periods – prenatal and postnatal.

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Prenatal hematopoiesis

During intrauterine development, the blood elements are produced in the liver, spleen and the bone marrow, and even in bones, in which the blood elements cannot be formed after birth. The bone marrow gradually forms all types of blood cells: red blood cells (they differ from erythrocytes that are formed after the birth and from those formed in the adulthood), lymphocytes and platelets. The ongoing development of medullar hematopoiesis leads to the cessation of hematopoiesis in other organs. During the prenatal period, the umbilical cord is a part of the blood circulation, which as well as the placenta is richly interlaced with many blood vessels. In these blood vessels at the time of the birth of a child is lodged and embedded portion of blood rich in stem cells - umbilical cord blood.

Postnatal hematopoiesis

After the birth, most of the blood elements are exclusively formed in the bone marrow. From here, due to their unique properties, the elements enter the circumferential (peripheral) blood. The white blood cells are produced in the short term in the spleen and thymus. A small portion of platelets is created in the lungs. Healthy bone marrow is therefore important and completely indispensable for our body.

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Bone Marrow

Bone marrow is a soft tissue that inlays the insides of bones of mammals and is one of the largest organs in the human body that takes up from 3.5 to 5.5% of total body weight. After the birth, the bone marrow is de facto the only place for hematopoiesis and produces several hundred billion blood cells every day, which are essential and necessary for our existence.

Practically, in all bones after the birth and in the childhood the red bone marrow is present in its active form. Its purpose is to produce hematopoietic cells. It consists of maternal and stems cells, precursors of blood elements, from which red and white cells, platelets, and mature blood elements are then formed. The bone marrow is interwoven with a network of blood vessels, which provide nutrients and serve as transport channels for the transmigration of blood elements into the bloodstream. There are also nerve fibers that almost certainly affect the production of hematopoiesis that is subject to the demands of the body. During the development of human body, part of the red bone marrow is replaced with inactive bone marrow fat. In adult humans, unlike in children, the active red bone marrow is present also in the vertebrae, ribs, sternum, pelvis, skull, clavicle, shoulder blades and parts of the thigh and the humerus. The most active bone marrow is present in the sternum and vertebrae.

These are cells that are able to differentiate the blood elements (red cells, white cells and platelets). In adult humans, they are found only in bone marrow. Scientific research and some clinical experiences have confirmed that only a blood stem cell under certain conditions is able to transform (differentiate) into cells of other tissues, and this is their great potential!

Bone marrow – is taken from the pelvic bone and it is in liquid form. There it can be found in quite large quantities and is rich in hematopoietic stem cells, however, the engraftment from the bone marrow takes longer to recover (because of the immunity of fully developed adults). Also through the aging process and undergone therapies the cells have a limited ability to divide. There is a need for absolute compatibility between the tissue characteristics of the recipient and the donor. The bone marrow is collected from donors between 18 and 35 years of age and under specific conditions. The collection of bone marrow is subject to donor health and his or her willingness to donate the bone marrow when asked by the clinic’s medical staff. Therefore, the registry of donors does not have bone marrow transplants standing by, but a list of potential donors, instead. Bone marrow donors are in extremely high demand and very much preferred. If you want to become a bone marrow donor – please see these websites for more information: www.kostnidren.cz/registr or www.czechbmd.cz.

Umbilical cord blood – is collected from the umbilical cord and placenta right after childbirth. Adaptation of the engraftment takes a little longer but is more successful. The stem cells have the maximum vitality and ability to be extensively fragmented. The disadvantage is that the umbilical cord blood has a relatively small number of hematopoietic stem cells, therefore they are used particularly for the treatment of pediatric patients. (Some grafts from umbilical cord blood can be used in connection with other grafts – this applies especially for allogeneic transplantation where these grafts support one another. Furthermore the progress of the methodology for "expansion" of stem cells has been developed according to specific needs and patient’s weight). Umbilical cord blood is not fully developed to be 100% immune – it is called "naive and immature". This allows the blood to be used for grafts with less comparable tissues of the donor and the recipient. With the autologous (own blood) cord blood grafts there is a blood match 1:1 (100% match between donor and recipient). In addition, the use of cord blood grafts from siblings is also common where matching tissue ratio stands at 1:4 (25% match between donor and recipient)!

Peripheral blood – is collected from the bloodstream after the stimulation of bone marrow with the growth hormone (G-CSF). The advantage of this medical action is a good adaptation of the engraftment and less stress on the patient, less than during the collection of bone marrow. Hematopoietic stem cells are collected from peripheral blood of the patient into a special machine, where the cells are trapped (so-called aphaeresis). The residual blood is again fed back into the patient.

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Stem cells from umbilical cord blood ...lear more

Umbilical cord blood is a source of several types of stem cells. It is known, since the 1970s  that in cord blood, like in bone marrow, there are hematopoietic stem cells in relatively large quantities.  These cells are currently used in the treatment of severe (life threatening) disease. Learn more in the Chapter Diseases treated by cord blood transplantation). Apart from these cells, there are also cells that are able to transform into other cell types (Pic.2), and thus these new venues have enabled their use in regenerative medicine and tissue engineering. These are in particularmesenchymal stem cells and stem-like cells similar to embryonic cells.

Mesenchymal stem cells are able to transform into various types of cells - the blood cells, muscle cells, bone cells, cartilage, liver cells, heart muscle cells, etc. Embryonic stem-like cells are also able to transform into various types of cells, and their ability to do so is much higher. According to Colin McGuckin, M.D. from Kingston University in UK, the discovery of these unique cells is one of a kind, due to exceptional combination of both stem cell quality and embryonic cells. All types of stem cells contained in umbilical cord blood, are the subject of intense research and their unique characteristics appear to have prospects primarily for use in the field of regenerative medicine. Only hematopoietic stem cells from umbilical cord blood are currently used within the frame of medical practice. Within the scope of clinical studies, aside from the field of hemato-oncology, autologous transplants from umbilical cord blood are primarily used for the treatment of pediatric patients with diabetes (diabetes mellitus) type 1 or hypoxic brain damage after birth. Other numerous findings in the field of regenerative medicine, list of their use, etc., can be found at:

http://parentsguidecordblood.org/content/usa/medical/autocbt.shtml?navid=32

Pic.2: Plasticity of stem cell from umbilical cord blood

In the treatment of certain serious illnesses, the only option is the administration (transplantation) of stem cells from a suitable healthy donor. At the crucial moment, in case of appropriate compatibility, a healthy sibling becomes a perfect donor. We talk about maximum compatibility success if the matching ratio reaches a quotient of 1:4 or 25%. The only condition for possible match of siblings is that they have the same parents, which “provide” the child with their tissue characteristics (three characteristics are inherited from the mother and other three from the father). Prepared transplant from an umbilical cord blood can help not only the child but also his or her sibling. Sampling and preparation of umbilical cord blood transplant is of great importance especially for those families where there is an illness treatable with a sibling’s hematopoeitic stem cell transplantation, and thus it increases the future chances for his or her survival. If you already know that your older child is seriously ill and a suitable donor cannot be found in other a way other than through the collection of umbilical cord blood of your upcoming child, please contact the umbilical cord blood Bank, which will perform this "indicated sampling” free of charge. (www.bpk.cz).

Own umbilical cord blood (autologous) transplant is currently used for treatment of diseases, where normally the bone marrow transplantation (autologous) is used.  Annually many developed countries around the world perform autologous bone marrow transplantations on more than 40 million people and their number is higher than the number of donated (allogeneic) transplants.

Using your transplant from your own umbilical cord blood is possible not only in childhood, but also in adulthood. With gaining years, the probability of transplant utilization increases due to higher occurrence of disease, for which the treatment involves the use of autologous hematopoietic cells. A recent study of American Scientists presents the calculation of the probability of ceding an autologous transplantation during human life at the ratio 1:400. This calculation was based on the frequency of the disease and the amount of transplants used for the treatment.  Until the 20th year of a person’s life, the probability that the child will undergo an autologous transplant is approximately 1:5000¹⁾. Current estimates for autologous transplant use include only diseases in which hematopoietic cells are used during conventional transplantation. Today there are already known results of new experimental studies in which autologous umbilical cord blood is very successfully used even for diagnoses such as Diabetes mellitus (diabetes) - type I Diabetes or traumatic brain disorders occurring at the birth. Use of stem cells and cord blood in these new areas of medicine greatly expands the possibilities of their use.

Source: 1.) Nietfeld at al.: Biology of Blood and Marrow Transplantation, 14:316-322, 2008.

This is a standard method of therapy primarily used not only in the treatment of hematological diseases but also in the treatment of solid tumors (myeloma, lymphoma) and mainly in the treatment of benign diseases. Today, thanks to modern methods these transplants are inserted into many patients at an earlier stage of the disease and thus reducing the risk of side effects. Nonetheless, a procedure is used for very serious and life-threatening diseases.  Like other methods of treatment, the stem cell transplantation affects the course of disease and subsequently the quality of patient’s life.

When bone marrow fails blood elements cease to be produced in the body: red and white blood cells and platelets. The aim of transplantation is the restoration of hematopoiesis in bone marrow. The success of transplantation depends on a suitable alternative source of healthy hematopoietic stem cells. Up to 50% of patients die because either they do not have any suitable donor or the transplanted hematopoietic stem cells are not sufficiently compatible or die due to other post-transplant complications (e.g. multiple organ failure).

A rerequisite for a successful transplantation is a consensus between the donor and the patient in HLA system (Human Leukocyte Antigen). Antigens in white blood cells are unique for every human being. Therefore, it is very difficult to find a suitable donor. To find a suitable - compatible - donor is particularly difficult and time-consuming.  Should there be no suitable donor within the family (sibling, mother, etc.) the proper donor must be looked for between unrelated donors in the registry.

If the patient does not have an autologous transplant (the stem cells’ donor is the patient himself or herself) it is necessary to determine the compliance of the tissue characteristics (HLA).  There are six characteristics monitored.  The perfect match is considered 6/6 ratio, however the bone marrow tolerance is 5/6 ratio.  The perfect match of tissue characteristics consequently reduces the probability of further complications (infection, bleeding, etc.).

Bone marrow, umbilical cord blood or peripheral blood is currently used as a source of hematopoietic stem cells. The source of hematopoietic stem cells used depends on many factors: type of disease, previous treatment methods, general health status, age, etc. The transplant committee, along with the doctor who performs transplantation, chooses the most appropriate source of stem cells, depending on the type of disease.  Transplantation of stem cells is currently performed to treat about 70 different diseases.