19 February 2009
Stem cell transplantation is considered by many to hold great hope as a potential treatment for all sorts of serious diseases and injuries. However, concerns have previously been confessed about safety, which is why trials of therapeutic transplantation are carefully regulated in many countries including the UK (but currently to a far lesser degree in countries such as Russia and China – see previous news), and why no technique is yet considered proven as both effective and safe.
One major concern has been that stem cells, by their very nature in having the capacity to proliferate, and to variable extents differentiate into different specialized cell types, might also give rise to tumours. Tumours arise from a single cell in which a series of mutations have arisen that deregulate the normal precise control over cellular growth and proliferation; loss of control leads to inappropriate or uncontrolled growth.
A new article published in the open access journal PLoS Medicine reports the case of a boy with ataxia telangiectasia who received three courses of injections to deliver fetal neural stem cells to his brain and stem cells from 2001 in a Russian hospital. Ataxia telangiectasia is a very rare recessively inherited genetic disease caused by the presence of mutations in the ATM gene, which cause damage to parts of the nervous system and result in progressively severe disability from early childhood onwards.
Two benign tumours subsequently developed in the boy’s brain and spinal cord. Surgical removal of the spinal cord growth in 2006 and genetic analysis by Israeli doctors revealed that it was derived from transplanted cells, containing two normal copies of the ATM gene, and including both male and female cells, having XY and XX chromosomes, respectively. HLA typing confirmed that the tumour included cells from at least two distinct (fetal) donors [Amariglio N et al. (2009) PLoS Med. 6(2) : e29]. This is the first example of tumours arising from transplanted donor stem cells, other than leukaemia in patients who have received hematopoietic stem cells, especially cells derived from umbilical cord blood as opposed to bone marrow [Greaves MF (2006) Leukemia 20(9):1633-4].
The spinal cord tumour had not recurred at the time of reporting, but the brain tumour has continued to show slow growth; although it has not been biopsied (a tissue sample removed), the researchers suggest that the tumours probably arose independently from transplanted cells injected at different sites, concluding that “the concerns raised regarding the risk of tumor development resulting from therapeutic transplantation of neural stem/precursor cells were not unfounded” and calling for more research into safety, in order to minimize the risks of stem cell therapeutics.
Comment: This finding is significant, supporting fears that stem cell therapeutics may retain the capacity to form tumour cells, and underlines the importance of properly regulated trials (including long-term patient follow-up) of novel treatments. However, all is not necessarily lost for stem cell transplantation. In the case of very serious debilitating diseases and injuries, a degree of risk (whilst strongly undesirable) may be tolerated by patients when weighed against the potential advantages of an otherwise efficacious treatment. The other potential mitigating factor is the nature of the disease in question; ataxia telangiectasia often results in a weakened immune system (see AT Society website), and this in itself could increase their propensity to develop tumours. The findings are therefore not necessarily directly applicable to other conditions for which stem cell transplantation has been used or suggested. Clearly, ongoing scrutiny will be required to assess the wider risk of tumours as the result of donor stem-cell transplantation.