The stem cells

What are the stem cells?  

They are cells which have the capacity for self-replication and the ability to differentiate (change) in a well controlled way to form highly specialized cells which built-up the various organs or tissues.

The stem cells are distributed in two major types and in relation to the source of their isolation and their repertoire for differentiation these cells are defined as two major types and namely embryonic stem cells (ESC) and adult (post embryonic) stem cells (ASC).

Adult stem cells include the hematopoietic stem cells (HSC) which can be isolated from bone marrow, blood from umbilical cord, peripheral blood), the mesenchymal stem cells (MSC) isolated from bone marrow, adipose tissue, Wharton jelly of the umbilical cord, skin stem cells, nerve stem cells etc.

Cell division is a basic physiological process and the stem cells are characterized by two possible forms of cells division and they are – symmetric division which is a process for self replication results in two identical cells which preserve the basic features of the stem cells and asymmetric division which results in two cells as one of them preserves the features of the stem cells while the other cell gets on the path of differentiation. In this process new sets of genes are activated, the cell acquires new specialized features specific to the functional mature cells. The differentiated cell is an element of a tissue or an organ capable to execute specific physiological act.

Why are stem cells so important?

Stem cells are the essence and the basis of regenerative medicine as they can be used for regeneration, reconstruction or building-up de novo of damaged organs or tissues in human body for medical or cosmetic purposes.

The main aims of this new direction of development in the medicine are quite numerous and include treatment of degenerative diseases of the nervous system (Parkinson’s disease, Alzheimer’s disease), cardiovascular diseases (heart infraction, atherosclerosis), oncology and hematological diseases (leukemia), endocrine diseases (diabetes), genetic diseases (thalassemia, Fanconi’s anemia), traumatic injuries and orthopedic diseases. Not less attention and efforts are devoted to the possibility to use stem cells for treatment of large skin defects after traumatic injury or burns as well as for cosmetic purposes. The list of pathologies treated by the methods of regenerative medicine is progressively increasing including new diseases. It is for the first time that science recognizes the possibility to use organism’s own “spare parts” to repair various damages and these means are the stem cells.

Hematopoietic stem cells (HSC)

Definition

Hematopoietic stem cells (HSC) have been characterized in deep details concerning the course and the stages of their differentiation according to the expression of specific markers at each consecutive step in their differentiation.   HSC are responsible for all self sustaining and self regulating functions of the hematopoietic system. A single HSC is capable of restoring the whole hematopoietic system of the organism with all its elements like lymphocytes, granulocytes, monocytes, erythrocytes etc. HSC possess the ability to differentiate rapidly into functionally active cells of the immune system such as dendritic cells, Nk cells, T- and B-lymphocytes.

Sources

At the late 80’s of the last century it was shown that human placental blood contains hematopoietic stem cells and thus it can replace the bone marrow as the classic source of HSC for transplantation.

The first case reported for application of cells from placental blood for medical reasons was the transplantation of such cell to a child with Fanconi’s anemia (1988) and this case report triggered the interest into placental blood cells. Generally the source of HSC for grafting is the bone marrow from genetically identical donor or allogeneic bone marrow from genetically closely related donor, or cell from the peripheral blood of the patient or placental blood.

Ideally the best donors would be identical twins, but this is possible in rare case for privileged patients.

The preparation of the donor by itself is a rather long process with the need to perform a number of hematalogical, immunological and virology tests which together with the other tests and collection of the bone marrow is a long process with higher cost for the patients. In cases of patients from ethnical minorities the probability to find a tissue competible donor is extremely rare. These are the reasons the placental blood to be considered as a cheaper, easy to use source for collection of HSC which makes the transplantation of blood cell much cheaper and suitable for broader applications.

Major advantages of placental blood as a source for collection of HSC

Using placental blood for isolation and transplantation of hematopoietic stem cells has a number of advantages in comparison to other source of HSC:

Advantages of the placental blood
Shortcomings of bone marrow
Collection of placental blood is a safe and technically easy procedure which absolutely safe for the mother and the newborn baby. The procedure takes about 2-3 min and can be begun just after the delivery of the baby. Collection of HSC from bone marrow is performed through a number of punctions of the hip bone which cause a lot of pain so that anaesthesia is needed with all possible risks.
Stem cells from umbilical cord blood (=placental blood) a more immamature (younger) which makes them more ready to differentiate i.e. they are more effective or a smaller number of cells is needed to achieve the desired therapeutic effect. Stem cell in the bone marrow have undergone more cycles of division and ageing in the adult organism. These processes diminish the capabilities of the cells for differentiation and make them less effective.
There is a much lesser risk for some transmissive infections because the risk of carrier is much lower in placental blood. Higher risk of some latent transmissive infections because of the life experience of the adult organism.
Placental blood contains higher numbers of stem cells and progenitor cells. Bone marrow of adults patients or children  contains rather low percentages of stem cells.
The rate and the severity of graft-versus-host reaction are much lower in cases with transplantation of HSC from placental blood as compared to transplantation of HSC from bone marrow.
Stem cells from placental blood are 100% compatible for the baby (the donor) so they can be used for safe autologous transplantation.

Applications

  • Diseases which are treated by transplantation of stem cells isolated from umbilical cord blood (placental blood):
  • Chronic leukosis;
  • Mielodisplastic syndrome;
  • Disease associated with pathologies of the stem cells – aplastic anaemia, Fanconi’s anaemia, paroxysmal night haemoglobulinuria;
  • Disease associated with proliferation of myeloid cell lineage – acute and idiopathic myelofibrosis, polycetemia verra, essential thrombocytemia;
  • Lymphoproliferative disorders – Hodgkin’s lymphoma and non-Hodkin’s lymphoma;[/gn_list]
  • Phagocytic dysfunctions;
  • Histocytic dysfunctions;
  • Inherited anomalies of erythrocytes – beta thalassemia, sickle cell anaemia;
  • Inherited disorder of the immune system;
  • Glanzmann’s Thrombasthenia;
  • Waldenstrom’s Macroglobulinaemia;
  • Other inherited disorders.

Mesenchymal stem cells (MSC)

Definition

Bone marrow comprises of three major cell systems – hematopoietic, endothelial and stromal cells as the last term designates cells which are not well defined but it is known that they support the haematopoiesis. When a suspension of bone marrow cells is cultured in vitro for longer periods fibroblast-like cells which adhere to the plastic are observed. Numerous studies have proved that these cells can be defined as mesenchymal stem cells (MSC) as they can differentiate in a number of cell lineages:

 

 

 

Sources

Mesenchymal stem cells (MSC) can be isolated from bone marrow, adipose tissue, Wharton’s jelly of the umbilical cord, placenta etc.

Possible or expected applications of MSC

So far MSC are supposed to be used as supplementary therapeutic means in treatment of:

  • Cardiocascular diseases such as heart infraction, cardiomyoplastia;
  • Damages and traumatic injuries of the nervous system;
  • Bone defects and breaks;
  • Osteoarthritis and damages of the cartilages;
  • Reconstruction of broad skin defects after injuries and burns;
  • Suppression of immune reactions after transplantation of cells or organs;
  • Modulation of the immune reactions in patients with autoimmune diseases;
  • Reconstruction of tooth defects;
  • In cosmetic medicine and plastic surgery