Bone Marrow Stem Cells
Bone marrow stem cells
Diseases such as aplastic anaemia, or infections (such as tuberculosis) can negatively impact the ability of the bone marrow to produce blood cells or platelets. Other diseases, such as leukaemia, also affect the progenitor/stem cells in the bone marrow and are diagnosed by a bone marrow biopsy where a sample of the tissue is taken using a large hollow needle inserted into the iliac crest (the pelvic bone). Harvesting bone marrow is usually done under general anaesthetic, although local anaesthetic is also a possibility.
Recent advances in stimulating and harvesting stem cells from the peripheral blood may mean that the invasiveness of bone marrow harvesting can be avoided for some donors and patients. Stimulatory pharmaceuticals, such as GM-CSF, and G-CSF, which drive the stem cells out of the bone marrow and into the peripheral circulation, can allow for a large yield of stem cells during apheresis. However, bone marrow stem cells have been found through research in the past five years or so to be able to differentiate into more cell types than previously thought. Mesenchymal stem cells from bone marrow have been successfully cultured to create beta-pancreatic cells, and neural cells, with possible ramifications for treatment of diabetes and neurodegenerative diseases. Clinical trials involving stem cell treatments for such conditions in humans remain theoretical however as there are a number of issues that need further investigation to confirm efficacy and safety.
Types of Stem Cells in Bone Marrow
The stem cells contained within bone marrow are of three types; haematopoietic stem cells, mesenchymal stem cells, and endothelial stem cells. Haematopoietic stem cells differentiate into both white and red blood cells, and platelets. These leukocytes, erythrocytes, and thrombocytes, respectively, play a role in immune function, oxygen transportation, and blood-clotting and are destroyed by chemotherapy for cancers such as leukaemia. This is why bone marrow transplants can mean the difference between life and death for someone suffering from such a disease as it is vital to replace and repopulate the bone marrow with stem cells that can then create new blood- and immune-forming cells.
Mesenchymal stem cells are also found in the bone marrow and are responsible for creating osteoblasts, chrondrocytes, and mycocytes, along with a number of other cell types. The location of these stem cells differs from that of the haematopoietic stem cells as they are usually central to the bone marrow, which makes it easier to extract specific populations of stem cells during a bone marrow aspiration procedure.
Bone marrow mesenchymal stem cells have also been found to differentiate into beta-pancreatic islet cells, with potential ramifications for treating those with diabetes (Moriscot, et al, 2005). Neural-like cells have also been cultured from bone marrow mesenchymal stem cells making the bone marrow a possible source for stem cell treatment of neurological disorders (Hermann, et al, 2006). More recent research appears to show that donor-heterogeneity (genetic differences between those donating the bone marrow) is at the heart of the variability in mesenchymal stem cells’ ability to differentiate to neural cells (Montzka, et al, 2009). This means that careful selection of donor stem cells would have to be carried out in order for treatment to be successful if the research ever displays clinical significance. Conditions such as spinal cord injury, Alzheimer’s Disease, and Multiple Sclerosis, may be able to be treated in the future using mesenchymal stem cells from bone marrow that were previously thought to only be able to produce bone and cartilage cell types.
Bone Marrow Transplants
Patients with leukaemia or other cancer are likely to be treated with radiation and/or chemotherapy. Both of these treatements kill the stem cells in the bone marrow to some degree and it is the effect that this has on the immune system that is responsible for many of the symptoms of chemotherapy and radiation sickness. In some cases, a patient with cancer may have bone marrow harvested and some stem cells stored prior to radiation treatment or chemotherapy. They then have their own stem cells infused after the cancer treatment in order to repopulate their immune system. This presents little risk of graft versus host disease which is a concern with, non-autologous, allograft bone marrow transplants. The use of a patient’s own stem cells is unlikely to be helpful in cases where an in-borne mutation of the blood and lymph system is present and such procedures are not usually performed in such cases.
Myeloablation and Stem Cell Therapy
Bone marrow transplantation from a donor source will normally require the destruction of the patient’s own bone marrow in a process called myeloablation. Patients who undergo myeloablation will lose their acquired immunity and are usually advised to undergo all vaccinations for diseases such as mumps, measles, rubella, and so on. Myeloablation also means that the patient has extremely low white blood cell (leukocyte) levels for a number of weeks as the bone marrow stem cells begin to create new blood and immune system cells. Patients undergoing this procedure are, therefore, extremely susceptible to infection and complication making bone marrow transplants only appropriate in life-threatening situations. Many patients will take antibiotics during this time in an attempt to avoid sepsis, infections, and septic shock. Some patients will be given immunosuppressant drugs to lower the risk of graft versus host disease and this can make them even more susceptible to infection.
Bone Marrow Transplant Problems
It is also possible that the new stem cells do not ‘engraft’, which means that they do not begin to create new blood and immune-system cells at all. Peripheral blood stem cells harvested at the same time as bone marrow harvesting were found in one study to speed the recovery of the patients immune systems following myeloablation, thus reducing the risk if infection (Rabinowitz, et al, 1993). Peripheral blood stem cells do appear to be quicker in general at engrafting and they may become more widely involved in the treatment of diseases traditionally addressed through bone marrow transplants (Lewis, 2005).
Continue Reading –> Cord Blood Transplants
References
Lewis A., Autologous stem cells derived from the peripheral blood compared to standard bone marrow transplant; time to engraftment: a systematic review., Int J Nurs Stud. 2005 Jul;42(5):589-96.
Rabinowitz AP, Watkins K, Groshen S, Chen SC, Rosen P, Mazumder A., Peripheral blood stem cells harvested during marrow recovery from disease-specific chemotherapy shorten duration of neutropenia in patients undergoing autologous bone marrow transplantation.Leuk Lymphoma. 1993 Apr;9(6):485-93.
Moriscot C, de Fraipont F, Richard MJ, Marchand M, Savatier P, Bosco D, Favrot M, Benhamou PY., Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro.Stem Cells. 2005 Apr;23(4):594-603.
Hermann A, Liebau S, Gastl R, Fickert S, Habisch HJ, Fiedler J, Schwarz J, Brenner R, Storch A., Comparative analysis of neuroectodermal differentiation capacity of human bone marrow stromal cells using various conversion protocols.J Neurosci Res. 2006 Jun;83(8):1502-14.
Montzka K, Lassonczyk N, Tschöke B, Neuss S, Führmann T, Franzen R, Smeets R, Brook GA, Wöltje M., Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression.BMC Neurosci. 2009 Mar 3;10:16.
