Haematopoietic Stem Cells Found In The Bone Marrow Biology Essay


The stem cells that form the myeloid and lymphoid cell lineages are known as the haematopoietic stem cells and are responsible for the constant renewal of blood. Haematopoietic stem cells are found in the bone marrow and are capable of giving rise to all blood cell types (multipotency), are self-renewing, can migrate out into the circulating blood from the bone marrow and they can undergo apoptosis which is programmed cell death (Wagers et al., 2002; Weissman et al., 2001).

Haematopoietic stem cells have long been harvested from the bone marrow. This is carried out by puncturing the hipbone, or in rare cases, the sternum with a needle under general or local anaesthetic. However, there are risks involved for the donor which include fatigue, low back pain, stiffness while walking, bleeding at the procedure site and complications from anaesthesia or injury to nerves, muscles, or bone (Burt et al., 2008; Kesselheim et al., 2009).

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Therefore, it is preferred to harvest cells from the peripherally, circulating blood. This is carried out by inducing the cells to migrate from the bone marrow into the blood by pre-treating the donor with cytokines, such as granulocyte colony-stimulating factors, that allow cells to be released from the bone marrow into the blood, then a few days later cells can be harvested from the blood (Sugarman et al., 1997; Cutler and Antin, 2001; Pulsipher et al., 2006). There are risks to donors for taking out peripheral blood stem cells, as they are exposed to the general anaesthesia, blood products and growth factors to mobilise haematopoietic stem, which may cause pain in the bone or headaches and there has been concerns about inducing leukemic transformation (Cutler and Antin, 2001; Pulsipher et al., 2006). However, the risk of serious harm is relatively low (Kesselheim et al., 2009).

Donors are at a lot more comfortable when collecting peripherally harvested cell since there is minimal pain, no anaesthesia, and no hospital stay and it yields better cells for transplantation. Moreover, studies suggest that patients that receive peripherally harvested cells have a better survival rate than bone marrow transplanted patients. This may be due to the peripherally harvested cells contains up to two times more haematopoietic stem cells than from the bone marrow. Also, it has been shown to engraft more quickly onto the patient (Laughlin, 2001; Leung and Kwong, 2010). This allows patients to recover their white blood cells, platelets, and their immune and clotting protection many days earlier than with a bone marrow transplant (Negrin et al., 2000). A major problem is that transplantations can cause graft-versus-host disease, in which the newly transplanted tissue attacks the patients' body (Cutler and Antin, 2001; Pulsipher et al., 2006; Laughlin, 2001). Researchers believe that some cells can be saved from the initial attack from the patients' suppressed immune system by using a larger graft (Beshlawy et al., 2009). Research currently done on mouse models supports the idea that purified haematopoietic stem cells engraft readily and show absence of graft-versus-host disease (Pulsipher et al., 2006; Verlinden et al., 1998). This study and studies alike may help eliminate graft-versus-host disease.

The placenta, the umbilical cord are rich sources of haematopoietic stem cells, and these cells are usually discarded as waste tissue so they can be collected without any medical or ethical issues concerning the mother or newborn baby (Beshlawy et al., 2009). Therefore, increasingly as a general or individual resource umbilical cord blood are harvested, frozen, and stored in cord blood banks. Cord blood transplantation has successfully been used in children. However, this is less frequent in adults as we are hardly ever able to remove more than a few million haematopoietic stem cells from a placenta and umbilical cord, and transplants for an adult ideally need 7 to 10 million cells per kilogram of body weight (Lickliter et al., 2000). Moreover, umbilical cord blood does also have its limitations such as the delayed immune development leaving patients more susceptible to infections for a longer period. However, umbilical cord blood is readily available, easy to harvest, reduced transmission of infection, able to store and less chance of graft-versus-host-disease (Laughlin, 2001; Koh and Chao, 2004). In addition, cord blood haematopoietic stem cells have been shown to have a higher proliferation than adult haematopoietic stem cells (Beshlawy et al., 2009). Several methods have been carried to overcome the cell number, including, with some success by combining several cord blood samples (Koh and Chao, 2004).

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Moreover, as already mentioned the low cell count in grafts limits the cord blood therapeutic effectiveness as it is associated with delayed or failed engraftment (Beshlawy et al., 2009). Scientists have shown there is a better chance of graft survival in patients when there is a larger number of stem cell in the graft. Therefore, being able to expand the number of human haematopoietic stem cells in vivo or in vitro would be an enormous advantage to all current and future uses of haematopoietic stem cells transplantation (Weissman et al., 2001; Burt et al., 2008).

The use of cord blood for transplantation has stirred a hot debate, as the general public fears of future research carried out on haematopoietic stem cells. For instance, embryo selection is used to create a related umbilical cord blood donor, this is done whereby embryos are conceived by in vitro fertilization, the embryos are analysed by pre-implantation genetic diagnosis to select a disease free or human leukocyte antigen matching the affected sibling, which are then implanted into the mother and conceived. Cord blood from the newborn is used to treat the affected sibling. But raises many ethical questions, such as are the parents willing to love and care the donor child as a family member or look at them as a hematopoietic stem cell donor. And even if the parents will love and care for the donor child, there are many risks the child will be exposed to. For example, if the umbilical cord blood transplant fails, parents often need to decide whether or not to harvest bone marrow stem cells from the new born, exposing the infant to procedure-associated risks. Parents face controversy as they must consider the interests both the healthy infant and the sick child (Grewal et al., 2004).

Regardless, the general consensus is that parents are in the best position to decide whether or not a young child should donate bone marrow to a sibling. The process of obtaining parental permission and child assent may include an independent assessment of the child donor's understanding, concerns, and willingness to donate (Pulsipher et al., 2006). However, the institutional review board does not allow these benefits to count as direct research benefits, regardless of their moral relevance (Grewal et al., 2004; Mychaliska et al., 1998). Some researchers therefore may feel that institutional review board should be more flexible about the regulations by approving research that seems ethical even when it does not actually meet regulatory requirements. However, allowing flexibility might ultimately allow approval of research that does not adequately protect human subjects (Mychaliska et al., 1998; Peerzada and Wendler, 2006). Moreover, the fact that ethical analyses of haematopoietic stem cells donation might be different between clinical and research settings is appropriate. Research is guided by the search for knowledge rather than the best interests of the subjects. Even when haematopoietic stem cells donation is ethically acceptable in the clinical setting, requiring it to satisfy research regulations as well ensures adequate human subject protection in the research setting (Mychaliska et al., 1998; Chan et al., 1996; Ross, 1994; Ross, 1993).

Requiring approval for transplant research that does not fit the minimal risk category with respect to the donor seems appropriate, especially given the conflicts of interest that parents might face when deciding whether to allow one child to participate in a transplant protocol in order to benefit another (Peerzada and Wendler, 2006). On the other hand, some may consider it too restricted in light of the lifesaving potential of transplant research and the fact that transplant donation within a research may be considered ethical in many circumstances (Kopelman and Murphy, 2004; Kopelman and Murphy, 2004).

The main application of haematopoietic stem cells in transplantation can be autologous or allogeneic. Autologous transplantations use the patients' own haematopoietic stem cells and so no host-versus-graft disease. The main drawback is the absence of a graft-versus-tumour in cancer patients treated with autologous tissue drafts. A graft-versus-tumour is phenomenon that allowed Immune system cells from a normal transplanted donor to recognise cancer cells of recipients' cells as diseased cells and destroy them (Brown and Boussiotis, 2008; Paulson et al., 2011).

Allogeneic transplantations occur between two individuals who differ in their human leukocyte antigens. The immune system uses human leukocyte antigens to distinguish between self and non-self. For a transplantation to be successful, allogeneic grafts must match most of the six to ten major leukocyte antigens between the host and the donor (Brown and Boussiotis, 2008; Ferrara et al., 1999). The benefit of allogeneic grafts is the graft-versus-tumour response, which contribute to maintaining and achieving complete remission (Brown and Boussiotis, 2008; Paulson et al., 2011).

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One of the first clinical uses of haematopoietic stem cells was the treating leukaemia and lymphoma, which are cancers of the blood (Paulson et al., 2011), leukaemia and lymphoma resulted from the uncontrolled proliferation of white blood cells. In this application, the patient's own cancerous haematopoietic cells are destroyed via radiation or chemotherapy, and then replaced with a haematopoietic stem cell transplant collected from the bone marrow or peripheral blood of a matched donor (Brown and Boussiotis, 2008). For the first time, many patients survived and did not die due to transmitted infection or graft-versus-host disease and the survival rate measured in years or even decades, rather than months. A recent strategy is transplantation using umbilical cord blood, allowing us to be able to expand the potential donor pool while reducing the level of graft-versus-host disease. Allogeneic haematopoietic stem cell transplants are also used in the treating hereditary blood disorders, such as sickle cell anaemia, Hunter's syndrome and aplastic anaemia. These disorders include sickle-cell anaemia, Hunter's syndrome and osteopetrosis (Brown and Boussiotis, 2008; Paulson et al., 2011).

Another application in cancer therapy, patients' haematopoietic stem cells are collected and stored while they undergo chemotherapy or radiotherapy to destroy cancer cells (Brown and Boussiotis, 2008). After the therapy, the patient receives a transfusion of their stored haematopoietic stem cells. Since patients receive their own cells, there is no chance of graft-versus-host disease. However, the issue with using autologous haematopoietic stem cell transplants in cancer therapy is that the cancer cells can sometimes be accidentally collected and re-infused back into the patient body along with the stem cells (Saiz and Graus, 2010).

Therefore my conclusion is that haematopoietic stem cells have seen widespread clinical use. New research and clinical discoveries means that haematopoietic stem cells holds a strong promise for treating autoimmunity, directing cancer therapy and generating tolerance for tissue-organ transplantation. However, many challenges remain for instance, eliminating host-versus-graft disease, decreasing graft rejection and the ability to expand and grow haematopoietic stem cells in ex vivo. With the possibility of ex vivo expansion of umbilical cord blood, some of the ethical issues raised in this field can be lessened.