human induced pluripotent stem cells in cancer treatment
-
Upload
university-of-kerala -
Category
Education
-
view
379 -
download
3
Transcript of human induced pluripotent stem cells in cancer treatment
Cancer
Diagnosed each year in one in every 250 men and one in every 300 women(WHO).
Clonal in origin
Six hallmarks
1. Immortality eg. HeLa cells
2. Produces GO signal, ie proto-oncogenic protiens
3. Override STOP signals (TSGs inactivation)
4. Resist cell death
5. Angiogenesis
6. Metastasis
Treatments available
Radiotherapy Chemotherapy Hormone therapy Cytokines Monoclonal antibodies Gene therapy
Gives rise to all type of cells present in an organism. E.g., embryonic stem cells derived from blastocyst
iPSCs were first produced in 2006 from mouse epidermal fibroblast cells
In 2007, iPSCs were derived from human cells by Shinya Yamanaka's team at Kyoto University, Japan
Nobel Prize in Physiology or Medicine for the discovery that mature cells can be reprogrammed to become pluripotent
Mouse iPSCs
Human iPSCs
Potentials of iPS cellsPotentials of iPS cells
Ability to differentiate into many cell types
Easily accessible
Individual-specific i.e. personalized or non-immunogenic
Vastly renewable
Useful for studying mechanisms of disease
Useful for drug, toxicity testing
Immunotherapy
• Immune system fails to effectively fight the tumor.
Tumor tolerence
Weak response
Defending property
• autologous immune enhancement
Dendritic cell vaccines(iPSDCs)
T-cell therapies
NK-cell therapies
Contd…..
• Antitumor monoclonal antibodies
block growth signals
stops angiogenesis
Drug/radiation delivery
• Cancer vaccines
Disease modeling
• Best model to study cancer pathogenesis is primary patient sample.
• iPSCs can be generated from cancer cells.
• Can use for
Pancreatic Ductal Adenocarcinoma(PDAC)
Chronic myeloid Leukemia(CML)
Juvenile Mylomonocytic Leukemia(JMML)
Obstacles in therapeutic application of iPSCs in humans
• Use of harmful oncogenes as part of the reprogramming factors.
• Use of viral vectors for gene delivery that carry the risk of insertional mutagenesis.
• Low efficiency and slow kinetics of reprogramming.
• Lack of robust and reliable differentiation protocols for human iPS cells
Conclusion
• Discovery of iPSC is a remarkable boost to research and therapy
• Offered a new field for cancer research and future possible applications in the clinical practice.
• use of hiPSCs may contribute to the development of future personalized cell therapies and open new possibilities
References1. Seung-Ick Oh, Chang Kyu Lee, Kyung Jin Cho,Kyung-Ok
Lee, Ssang-Goo Cho, and Sunghoi Hong; Technological Progress in Generation of Induced Pluripotent Stem Cells for Clinical Applications, The Scientific World Journal ,10 (2012),1-10
2. MartinezMatthias Stadtfeld and Konrad Hochedlinger; Induced pluripotency: history, mechanisms and applications, Genes & Development, 24 (2010), 2239–2263
3. Timothy J Nelson, Almudena , Fernandez, SatsukiYamada,Yasuhiro Ikeda, Carmen Perez-Terzic, Andre Terzic; Induced pluripotent stem cells: advances to applications, Stem Cells and Cloning: Advances and Applications,3 (2010), 29-37
4. Eamon Geoghegan and Lucy Byrnes; Mouse induced pluripotent stem cells, The International Journal of Developmental Biology, 52, (2008), 1015-1022
5. Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita,Tomoko Ichisaka, Kiichiro Tomoda and Shinya Yamanaka; Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors,Cell, 131, (2007), 1–12