Forsøksdyr: Human niche environment for the understanding and treatment of leukaemic disease

Godkjenningsdato 24.04.2018

The bone marrow microenvironment has a critical role in the leukaemic disease development. To improve the understanding of the leukemogenesis and heterogeneity of leukaemic diseases, we intend to create an extra-medullary bone marrow niche, that explore the engraftment of the leukemic diseases such as MDS and AML that have lower engraftment potential. We aim in this study to utilize this model to investigate novel therapeutic modalities. Further on, we will focus on the heterogeneity of both AML and MDS in our models, compared to traditional patient derived xenogaft (PDX).

Anticipated adverse effects on the animals: Our planned experiments must be classified as procedures of moderate severity: implantation of human cells will be performed subcutaneously, under anaesthesia and we expect the tumor to grow up to 0.5 cm. Engraftment of human cells will be monitored by optical imaging and blood sampling. Animals will develop leukaemia with clinical signs as weight loss and anaemia.

In this study we plan to use 544 male and female NSG and NSGS immunodeficient mice with over 10 multi-component studies.

In conclusion this will possibly establish more efficient, relevant and more successful preclinical studies of Leukaemic diseases. That in turn will result in a higher understanding of leukaemogenesis and the bonemarrow microenvironment. Lastly having a relevant model, able to recapitulate the various leukaemias and thus develop targeted therapies that can be translated to patient care. The only in vitro alternative is the use of cell lines and primary patient material in culture. However, these results do not always evaluate systemic toxic or efficacy effect, thus the use of animal models is unavoidable.
The smallest possible groups to provide a statistically significant power will be used for these experiments.Optical imaging provides more qualitative analysis where tumor burden can be followed longitudinally in a spatiotemporal manner, and also allow us to follow disease and therapeutic efficacy in a manner unprecedented, while permitting imaging of molecular and anatomical disease staging.
Experienced technicians will monitor the animals and they will very early discover any sign of illness and take the decision of euthanasia.