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10.1 How do we differentiate pluripotent, multipotent and unipotent stem cells?
Pluripotent and multipotent stem cells can make several different cell types whereas unipotent cells can only make one type of cell. However, pluripotent stem cells are differentiated from multipotent stem cells, in that pluripotent can make all cells of the body (with the exception of the placenta and embryonic sac of the foetus) and multipotent cells can only make several cell types from one lineage (for example a multipotent liver stem cell can make all the cells of the liver but can’t make blood cells).
10.2 What is the difference between haematopoietic and mesenchymal stem cells? What different cell types do the make?
Both haematopoietic and mesenchymal stem cells reside in the bone marrow space, but mesenchymal stem cells make up the bone marrow (stromal) microenvironment whereas the haematopoietic stem cells make up the blood system.
Mesenchymal cells produce the stromal layer of the microenvironment and do this by differentiating into adipocytes, osteoblasts and chondroblasts. Haematopoietic stem cells produce all the cells of the blood system which includes the lymphocytes (T and B cells, and NK cells), myeloid cells (neutrophils, eosinophils, basophils, monocytes and macrophages), red cells (erythrocytes) and platelets.
10.3 How do we harvest the different haematopoietic cells from the donor?
There are three sources of haematopoietic stem cells for donation, bone marrow, peripheral blood mobilised and umblical cord blood. Bone marrow derived stem cells are collected/aspirated under general anaesthetic from the posterior iliac crest of the hip using a needle. However bone marrow stem cells can be mobilised into the peripheral blood using growth factors (G-CSF) and Plerixafor, and then these stem cells can be collected by apheresis of the peripheral blood. Umbilical cord blood is collected after the baby has been delivered and the umbilical cord is cut; the placenta and cord are typically raised so that gravity aids in collection, and a needle is inserted into the umbilical vein to draw off the blood.
10.4 What is the difference between autologous, allogeneic and syngeneic transplants?
Autologous transplants describes the donor and recipient as being the same person, where tissue is collected and replaced (e.g. blood or bone marrow) or moved from one place to another on the same person (e.g. skin grafts). Where the donor and recipient are different people these may be either syngeneic or allogeneic transplants with the difference between these two dictated by genetic disparity/differences. Thus syngeneic transplants occur between identical twins who by definition are different people and yet genetically identical, whereas allogeneic transplants occur between people who are genetically different. Allogeneic donors could be a sibling, a parent or someone completely unrelated (but tissue type matched) to the recipient.
10.5 Why do patients need conditioning therapy before they receive their stem cell donation?
The main reason for conditioning therapy is to treat the haematological condition that the patient is suffering from so that it does not interfere with the transplanted stem cells. The coneditioning therapy thus serves three purposes; to deplete the marrow of malignant or diseased tissue, to make space for incoming stem cells, and to confer some immunosuppression on the patient so that they don’t reject the incoming cells.
10.6 Why might cord blood stem cells be considered superior to adult stem cells for transplantation?
Cord blood offers lots of advantages over adult stem cells such as bone marrow or peripheral blood derived stem cells. Firstly, collection of umbilical cord is less invasive to the donor as the donor is not affected, and similar numbers of CD34+ cells are obtained from the cord blood as the bone marrow. However cord blood cells have a higher proliferative potential, last longer and have greater haematopoietic cell colony production. Cord blood cells also respond more efficiently to cytokines and because they are immunologically more naïve they are less likely to produce a graft versus host disease response. Evidence suggests that cord blood is less likely to be contaminated with viruses too, and reduce the recurrence of leukaemia.
10.7 What are the range of complications we see with HSCT and when do they typically occur post-transplant?
There can be short term and long term complications for HSCT. Short term complications may be considered to occur within the first few weeks to months post transplant, whereas the long term complications may occur between a year to several years later. Short term complications include issues related to conditioning therapy such as gastro-intestinal disturbances (nausea, vomiting, diarrhoea, loss of appetite), tiredness, haematological disturbances (anaemia, immunosuppression, bruising from low platelets). Short term complications may also include graft failure and acute graft versus host disease.
Long term complications include chronic graft versus host disease, and complications form the genotoxic chemotherapy such as infertility, early menopause in women, cataracts and therapy related and donor cell malignancies.
10.8 What are the two novel approaches to the use of stem cells for personalised therapy?
The two main approaches for the use of stem cells is either to use them directly for transplantation purposes to replace diseased bone marrow tissue or to harness the plasticity of the stem cells by placing them in alternative environments which have the capacity to change their functionality and phenotype into the tissue that needs replacing.