2016 - £5000
University Of Newcastle
We have supported the work towards better understanding and treatment of the Aplastic Anaemia.
Below you will find a summary of the work
Severe Aplastic Anaemia (SAA) is a rare but serious illness, where the bone marrow fails to produce essential blood cells. All blood cells in the bone marrow are produced from stem cells.
In SAA however, these bone marrow stem cells are replaced by fat cells, leading to an underproduction of blood cells.
The causes of SAA, are unknown in the majority of cases. To date there are two models for explaining the stem cell loss in SAA:
(1) activation of immune system which attacks stem cells;
(2) or a failure to produce or maintain the haematopoietic stem cells.
As there are so few stem cells in the marrow of SAA patients, it has been very difficult to study stem cell function in this disorder.
To rectify this problem, we have taken skin cells from four patients and three unaffected individuals and we have turned them into stem cells which can form multiple cell types, including blood-forming cells.
Using this model in the lab, we have been able to show that hematopoietic progenitors derived from the SAA patients have a reduced ability to give rise to erythroid/megakaryocytic cells as well as showing a reduced number of multi-potent hematopoietic progenitors which would strongly suggest a “hematopoietic stem cell” defect in these patients. We now propose to use this patient specific disease model to study the impacts of existing curative therapies and the role of the immune system in development of SAA.
We strongly believe that such studies will lead to improved diagnosis and clinical management of SAA
Therefore we would like to focus on 3 key questions:
- What are the reasons behind the “hematopoietic stem cell defect” observed in SAA patients? Is this due to a reduced ability of these cells to proliferate? Are these cells more prone to dying? Do they have any abnormalities in their chromosomes (for example shorter telomeres)? Do they accumulate more DNA damage during their life span and if yes are they less able to repair this damage?
- How does addition of Eltrompobag affect the hematopoietic stem cells derived from the SAA patients? Does this also affect cells that are destined to become erythrocytes and megakaryocytes? Does addition of Eltrompobag rescues the hematopoietic stem cell defect that we have observed?
- How does activation of immune system (mimicked in our system through the addition of Myelo-suppresive cytokines) affect the hematopoietic stem cells derived from the SAA patients? Does this also affect cells that are destined to become erythrocytes and megakaryocytes? Does activation of immune system exacerbates the hematopoietic stem cell defect that we have observed?
2015 - £5000
Anthony Nolan Trust
investigating broader therapeutic uses of cord blood, and particularly looking at the functional integrity of stem cells harvested from cord blood and how this may affect their use.
Investigating different cord blood processing methodologies, we will test the sensitivity of samples and the impact of their clinical quality (i.e. their viability and potency) on the likelihood of achieving successful engraftment after transplantation. This will give us a better understanding of the engraftment process and a practical application as it will help us to update the tests we use to predict transplant outcome.
We will also look at the isolation of cell subsets (for example T cell therapies) and again the impact that each of these could have on improving transplants and their outcomes. In fact, we hope to be able to establish a protocol on the use of these therapies that will potentially inform alternative, safer and more effective transplant models.
The generous grant of £5,000 from the Anthony Booth Trust will purchase the consumables required by the project, particularly the reagents used to perform the isolations, and lease the equipment required to perform cell chromatography.
We expect to have some definitive conclusions from the study sometime in summer 2015 once all the analysis has been completed,
2013 - £5000
Anthony Nolan Trust
This increased capacity and efficiency will be essential as we open new cord collection centres around the UK, and the numbers we need to process in Nottingham continue to grow. We currently collect cords at King’s College Hospital in London, Leicester General Hospital and Leicester Royal Infirmary, and in all three we have recently scaled up our collection service to cover 24 hours/day, seven days/week. In early 2012 we will open two more centres at Birmingham Women’s Hospital and the Royal Free Hampstead.
2012 Why Research
When a baby is born, the placenta and umbilical cord that attached the child to his or her mother are usually just thrown away as of no further use – when in fact nothing could be further from the truth. The blood they contain has unique properties. It can be used to replace damaged bone marrow or for research that could lead to the successful treatment of a host of other diseases and conditions. Cord blood contains high levels of stem cells that can renew bone marrow and can regenerate the immune system. Because they come from a newborn infant, these stem cells are ‘naïve’ and able to change, and this increases their potential for developing new treatments. Through research, cord blood opens up a whole new future of possibilities of tissue transplantation and regenerative medicine. What’s more, cord blood is easy to collect and there is no risk to the baby or mother. By saving cord blood for banking and research, We have teamed up with e Anthony Nolan Trust Cord Blood Bank who will be able to save the waste of this amazing resource, and save the waste of thousands of lives.
They will be undertaking research primarily to improve the outcomes for transplant patients and improve life chances for those people suffering with blood disorders.