STEMEXPAND

Stem Cell Expansion - Expansion and engraftment of haematopoietic and mesenchymal stem cells

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 Obiettivo del progetto (Objective)

'Serious disorders of the blood system, particularly malignant blood disorders and genetic diseases can be effectively treated by blood and marrow transplantation. Despite considerable success with this treatment modality during the last decades, lack of suitable donors, engraftment failure and graft versus host disease remain serious problems that need to be addressed. This project aims to address these issues through approaches that will allow expansion of human umbilical cord blood stem cells for transplantation using cytokines, developmental cues, newly identified stem cell regulators and chemicals that can activate internal stem cell regulators to stimulate self-renewal and proliferation of hematopoietic stem cells. Successful expansion of cord blood stem cells will increase the number of hematopoietic stem cells in cord blood samples to generate suitable donor samples for adult patients that die from their disease today due to lack of donors. Expansion of hematopoietic stem- and progenitor cells will also give more efficient early engraftment following transplantation and thereby reduce the frequency of morbidity and mortality due to insufficient engraftment. This will be accomplished through the identification of novel stem cell regulators and the use of known cytokines, developmental cues and chemicals that will stimulate stem cell expansion. Improvement in hematopoietic stem cell transplantation through co-transplantation of mesenchymal stem cells will also be investigated. Conditions for expansion of mesenchymal stem cells will be defined and subsets of more primitive and more mature mesenchymal stem cells will be identified. Mesenchymal stem cells will also be used to improve engraftment efficiency of the expanded hematopoietic cells and to reduce the frequency of graft versus host disease. The findings are expected to have a great impact on the treatment of serious blood disorders by blood and marrow transplantation in the future.'

Introduzione (Teaser)

Blood and marrow transplantation are effective treatment for disorders of the blood system. But there are challenges when it comes to finding donors and grafting successfully.

Descrizione progetto (Article)

Medical research is looking for more efficient ways to avert complications and serious health issues that can arise with transplantation. The major issues that need to be addressed in this quest are the lack of suitable donors, failed grafting, and graft versus host disease.

The EU-funded project 'Stem cell expansion - expansion and engraftment of haematopoietic and mesenchymal stem cells' (Stemexpand) is working to find ways of increasing the number of human hematopoietic stem cells from umbilical cord blood and also of mesenchymal stem cells (MSCs). These can be used for transplantation in cases of blood disorders such as leukaemia.

The approach will put in action stem cell regulators that can stimulate self-renewal and an abundance of hematopoietic stem cells. In the case of cord blood samples, this will generate suitable donor samples and drive down mortality due to lack of donors. It will also allow for better short-term and long-term engraftment after transplantation, which will reduce complications and increase successful outcomes.

Researchers are also studying how to improve hematopoietic stem cell transplantation by co-transplanting MSCs. The project aims to define the conditions under which they can be expanded. Their use also has potential for reducing the frequency of graft versus host disease.

They Stemexpand team has discovered factors which boost stem cell survival. They succeeded in delineating genes and important pathways for stem cell regulation and have singled out 12 short hairpin RNAs (shRNAs). Usually used to silence gene expression, for the purposes of this study they show promise in being able to radically expand hematopoietic cells in culture. Bone marrow MSCs have been characterised and compared among various surgical procedures.

The project members are now trying to secure approval in France for a phase I transplantation trial that will use expanded umbilical cord blood stem cells. Two pre-clinical trials have already been performed, and others are underway.