Stem Cells & Haematopoietic Stem Cell Transplants

Stem Cells and Haematopoietic Stem Cell Transplants

 

 

 

 

Video: What are Stem Cells Transplants

 

 

Stem cells are cells found in most, if not all, multi-cellular organisms and are considered the basic blocks of life. They are responsible for the creation of all different types of cells in the body through their ability to differentiate. The two broad types of mammalian stem cells are: embryonic stem cells that are isolated from the inner cell mass of blastocysts, and adult stem cells (for example haematopoietic stem cells) that are found in adult tissues. In adult organisms, stem cells act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of regenerative organs, such as blood, skin, or liver.  Highly plastic adult stem cells from a variety of sources, including umbilical cord blood and bone marrow, are routinely used in medical therapies. 

 

Haematopoietic stem cells

There are three main sources of haematopoietic stem cells:

  • Bone marrow
  • Peripheral blood (blood that circulates through the body)
  • Umbilical cord blood 

Haematopoietic stem cells (HSCs) are multipotent stem cells that give rise to all the blood cell types including myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (T-cells, B-cells, NK-cells).

 

A hematopoietic stem cell is a cell isolated from the blood or bone marrow that can renew itself, can differentiate to a variety of specialized cells, can mobilize out of the bone marrow into circulating blood, and can undergo programmed cell death, called apoptosis—a process by which cells that are detrimental or unneeded, self-destruct.

 

 

 

 

What is a haematopoietic stem cell transplant?

 

Haematopoietic stem-cell transplantation is the standard therapy for many cancers that originate in the blood and bone marrow. This transplantation procedure involves exposure of the patient to chemotherapy or chemoradiation to kill cancer cells. This is followed by infusion of haematopoietic stem cells used as a graft. The purpose of this graft (haematopoietic stem cells obtained from bone marrow, peripheral or umbilical cord blood) is to reconstitute (reconstruct) the patient’s bone marrow and immune system.

 

 

Figure obtained from Juliet N. Barker and John E. Wagner (2003) Umbilical-Cord Blood Transplantation For The Treatment Of Cancer, Nature Cancer Reviews (3) 526-532

 

 

 

Treatment regimen and factors influencing the outcome of haematopoietic stem-cell transplantation.

 

Patients who receive stem-cell transplants for haematological disorders are first treated by a regimen of chemotherapy or chemoradiation. The regimen (course of action) that is, the duration and the strength of chemotherapy and radiation depend on the type of disease to be treated. The above figure is an example of such a treatment for a period of up to 7 days (starting at day –7 on the therapeutic timeline). The patients then receive either autologous or allogeneic haematopoietic stem cells (day 0 on the timeline). Patients also receive immunosuppressive drugs to prevent rejection of the transplanted cells.

 

Either AUTOLOGOUS haematopoietic stem cells (collected from the patient before treatment) or ALLOGENEIC haematopoietic stem cells (collected from a related or unrelated donor) can be transplanted.

The widespread use of allogeneic haematopoietic stem-cell transplantation has, however, a number of important limitations. These include

  • shortage of available matched sibling or matched unrelated marrow donors
  • the length of the unrelated marrow search process (which averages 4 months)
  • the risk of developing GRAFT-VERSUS-HOST DISEASE (GvHD). 

For a graft to be used it should be fully compatible to the patient, that is the donor and the recipient must have specific identical genes MAJOR HISTOCOMPATIBILITY ANTIGENS (also known as HLA MATCHING) so that the patient’s body accepts the graft as if it were its own.

 

This does not apply when the graft originates from the patient’s body (autologous) and the graft is not recognized as a foreign body, hence there is no rejection and risk of GvHD.

In cases of allogeneic transplantation despite of having a full match, there is always the risk of developing GvHD ranging from mild to severe, which may result to graft rejection.

 

Human leukocyte antigen (HLA) matching is required to prevent the devastating immune complications of graft rejection, GvHD and slow or incomplete immune reconstitution.

 

In order to prevent GvHD, medication is given to the patient to lower immune response (immunosuppresion) and prevent the body from attacking the graft. As a consequence, the body cannot fight infections due to immunosuppresion and such infections may be lethal to the patient.

 

When in search of a donor, physicians always seek to find a perfect match through members of the patient’s family, i.e. siblings (brother/sister). The chance of a patient’s full sibling being HLA identical is one in four. With increasingly restricted family sizes, only 30% of patients have a sibling donor who is a perfect match. Bone-marrow registries, which list more than 10 million volunteer donors worldwide, as well as public cord blood banks, have been created to help patients find suitable stem cell donors.

 

Despite the extent of the registries one out of three patients in need of a transplant is unable to find a suitable donor with a compatible graft obtained from bone marrow stem cells.

 

Therefore, umbilical cord blood is considered as an alternative graft, rich in haematopoietic progenitor cells.

 

 

Reference:

Juliet N. Barker and John E. Wagner (2003)Umbilical-Cord Blood Transplantation For The Treatment Of Cancer, Nature Cancer Reviews (3) 526-532