Welcome to the. 1 st workshop: Drawing lessons from stem cells and animal models outside the radiation field

Transcription

1 Welcome to the 1 st workshop: Drawing lessons from stem cells and animal models outside the radiation field

2 Context of the workshop Long-term animal studies have played fundamental roles for studies on radiation effects providing important complementary data to those obtained from human epidemiological studies. 2

3 Objective of the workshop - To integrate research activities outside the radiation protection field to promote continuing development of suitable whole animal models for radiation carcinogenesis and non- cancer diseases at low doses which bear clear relationships to human diseases. - To integrate current knowledge on stem cells models into radiobiological studies at low doses. 3

4 Definitions Stem cells - biological cells found in all multicellular organisms - that can divide (through mitosis) and differentiate into diverse specialized cell types - that can self-renew to produce more stem cells. 4

5 In mammals, 2 broad types of stem cells: - embryonic stem cells, which are isolated from the inner cell mass of blastocysts - can differentiate into all the specialized cells (called pluripotent cells ), - maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues - adult stem cells, which are found in various tissues. - act as a repair system for the body, replenishing adult tissues. 5

6 Definitions Animal models: An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of harming an actual human being during the process. 6

7 Definitions The animal chosen will usually meet a determined taxonomic equivalency (vertebrate, mammal, primate) to humans, so as to react to disease or its treatment in a way that resembles human physiology as needed. Animal models of disease: may have an existing, inbred or induced disease or injury that is similar to a human condition 7

8 Our starting point: Melodi SRA: Stem cells and animal models - Important to determine relevant molecular and structural changes induced uniquely by ionising radiation directly and that are in the long term persistent and contributing to cellular, tissue and organ dysfunction. The roles of different cell types, stem cells, progenitor and germ cells will need to be defined. 8

9 Melodi SRA - The identification and the nature and number of target cells at risk for specific cancers and non-cancers in humans are important questions. The target cells are likely to be stem cells or at least relatively early progenitor (little differentiated) cells. 9

10 Stem cells and animal models in Melodi SRA - For the detection of individual sensitivity, research should cover the following items: - sensitivity of different cell types (stem cells and progenitor cells) in different tissues (diseases). - establishing the range of radiosensitivity, genetic and epigenetic profiles - DNA repair capacity, capacity to undergo radiationinduced death - immunological, hormonal, inflammatory, general health status of radiation sensitive and resistant individuals. - latencies for different pathologies (cancer, non-cancer diseases). 10

11 Stem cells and animal models in Melodi SRA - The long-term priorities include the following areas: for radiation-induced cancers and non cancer diseases? Continuing development of suitable whole animal as well as human cellular models (including somatic stem cells) for radiation carcinogenesis and non- cancer diseases which bear clear relationships to human diseases. 11

12 Stem cells and animal models in Melodi SRA The combination of modelling efforts and animal, cellular and epidemiological data applying systems biology approaches will provide further insights into biological effectiveness of radiation quality. - Continuing development of suitable whole animal as well as human cellular models (including somatic stem cells) for radiation carcinogenesis and non-cancer diseases which bear clear relationships to human diseases.

13 Objectives: recommendations and roadmap for future studies - A list of existing studies with recommendations for key animal models. - Animal models will be selected to assess diseases of relevant tissues and organs, including the immune and hematopoietic systems, gastrointestinal tract, lung, kidney, heart, brain and skin following exposure to low dose radiation. 13

14 Objectives: review, roadmap and workshop - A roadmap for collaboration where appropriate agreements to set up for future collaboration. - Identification of non-nuclear laboratories with experience in animal models that are adaptable to radiation research to be seeked and future collaboration to be developed. - A review article - Workshops with stake holders in the field of radiation and non-radiation biology to bring scientists from other disciplines in specific key areas of RP research (animal models, stem cells). 14

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16 New animal building at SCK CEN since early

17 Our tasks 17

18 Typical questions to be addressed during the discussion after each session Q1: Emerging from non-radiobiology field, what are the best models so far to study this disease? Q2: Emerging from non-radiobiology field, do we have sufficient evidence from existing animal and stem cell experiments? Q3: For this particular disease, which animal and stem cell studies should be given priority and what should their objectives be? 18

19 Q4: For this particular disease, which types of animal and stem cell studies are uninformative or likely to be confusing and should therefore not be supported? Q5: Which experimental designs and which models (in vitro, in vivo, ex vivo) are suitable to study vascular, cognitive, cancer, embryological, immunological effects? 19

20 Q6: Which biological (in vitro) samples/culture types/conditions might be the most informative to further study this disease? Q7: For cancer and non-cancer diseases, which duration of experiments (short-, mid-, long-?) and which endpoints should be given priority? Q8: For these diseases, what are the likely cellular targets? 20

21 Q9: What are the experimental strategies to investigate the progression of the various diseases? Q10: Which are the driving mechanisms that should be explored to improve understanding of the development of the disease? Pathways and processes of systemic, local and multi-organ effects? Types of tissue? Accelerated aging/others biological processes or specific mechanisms? 21

22 Timeline Timing 2014 June 2014: 1 st workshop: defining very general recommendations September 2014: deliverable to be submitted (Month 28) October 2014: Report at Melodi workshop, Barcelona Timing nd Workshop on defining deeper recommendations Finalisation through a review article 22

23 Structure of the day - Cognitive Coffee break and group picture - Immuno - Cancer - Embryo Lunch Coffee break - Space - Cardio-vascular Farewell drink 23

24 Thank you in advance for your cooperation! All presentations will be placed on the workshop website. 24