Stem cell technology

Stem cell technology is a rapidly developing field that combines the efforts of cell biologists, geneticists, and clinicians and offers hope of effective treatment for a variety of malignant and non-malignant diseases. Stem cells are defined as totipotent progenitor cells capable of self renewal and multilineage differentiation.1 Stem cells survive well and show stable division in culture, making them ideal targets for in vitro manipulation. Although early research has focused on haematopoietic stem cells, stem cells have also been recognised in other sites. Research into solid tissue stem cells has not made the same progress as that on haematopoietic stem cells. This is due to the difficulty of reproducing the necessary and precise three dimensional arrangements and tight cell-cell and cell-extracellular matrix interactions that exist in solid organs. However, the ability of tissue stem cells to integrate into the tissue cytoarchitecture under the control of the host microenvironment and developmental cues, makes them ideal for cell replacement therapy. In this overview, we briefly discuss the current research and the clinical status of treatments based on haematopoietic and tissue stem cells.

Stem cells are progenitor cells that are capable of self renewal and differentiation into many different cell lineages

Stem cells have potential for treatment of many malignant and non-malignant diseases

Peripheral blood stem cells are used routinely in autologous and allogeneic bone marrow transplantation

Gene transfer into haematopoetic stem cells may allow treatment of genetic or acquired diseases

Embryonic stem cells may eventually be grown in vitro to produce complex organs

Neuronal stem cells are being used for neurone replacement in neurovegetative disorders such as Parkinson's and Huntingdon's diseases

Haematopoietic stem cells are a somatic cell population with highly specific homing properties and are capable of self renewal and differentiation into multiple cell lineages.2 Human haematopoietic progenitor cells, like stromal cell precursors in bone marrow, express the CD34 antigen, a transmembrane cell surface glycoprotein identified by the My10 monoclonal antibody.3 However, pluripotent stem cells constitute only a small fraction of the whole CD34+ population, which is by itself rather heterogeneous regarding phenotype and function. The best way to define haematopoietic stem cells is from their functional biology. They are known to restore multilineage, long term haematopoietic cell differentiation, and maturation in lethally cytoablated hosts.4 Haematopoietic stem cells can be obtained from bone marrow, peripheral blood,5 umbilical cord blood,6 and fetal liver.7

The use of peripheral blood stem cells in both autologous and allogeneic transplantation has become routine as they can be collected on an outpatient basis and also promote a consistent acceleration in haematopoietic reconstitution after engraftment.8 Umbilical cord blood stem cells have been used progressively in paediatric patients, from both related and unrelated HLA-matched donors. In recipients with severe T cell immunodeficiency disorders, fast engraftment is required together with a low risk of graft versus host disease and a low viral transmission rate.9 Since umbilical cord blood stem cells can be expanded in vitro or frozen for storage in cell banks10 they have been used in clinical trials for both autologous and allogeneic haematopoietic stem cell transplantation.11

The bone marrow is a mesenchyme derived tissue consisting of a complex haematopoietic cellular component supported by a microenvironment composed of stromal cells embedded in a complex extracellular matrix.12 This extracellular matrix has an important role in the facilitation of cell-to-cell interaction, in addition to a more complex role in the binding and presentation of cytokines to the haematopoietic progenitor cells.13 The cytokine milieu and extracellular matrix interaction provides the road map for maturation and differentiation of stem cells,14 which should be instrumental for their in vitro manipulation before therapeutic use. For example, haematopoietic stem cells can be manipulated in vitro to generate dendritic cells, the most potent antigen presenting cells.

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Stem cell technology

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