Dr Darius Widera Lecturer (Assistant Professor) in Stem Cell Biology...

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2 nd International Symposium “Age of Regenerative Medicine” 14 th May 2015, Stavropol, Russian Federation Dr Darius Widera Lecturer (Assistant Professor) in Stem Cell Biology and Regenerative Medicine

Transcript of Dr Darius Widera Lecturer (Assistant Professor) in Stem Cell Biology...

  • 2nd International Symposium “Age of Regenerative Medicine”14th May 2015, Stavropol, Russian Federation

    Dr Darius WideraLecturer (Assistant Professor) in Stem Cell Biology and Regenerative Medicine

  • What are Stem Cells?

    “Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.”

    NIH Stem Cell Info

  • What are Stem Cells?

  • The Promise of Stem Cell Research

    The Fountain of Youth, 1546 painting by Lucas Cranach the Elder

  • Stem Cells: Mysterious Cure for any and every disease?

  • The Aim of Stem Cell Research

    Modified from NIH Stem Cell Info

  • Developmental Potential of Stem Cells

    Modified from Hochedlinger et al

  • • Safety (high genetic stability, no tumour formation)

    • High developmental potential(regeneration of more than one cell type)

    • Potential autologous application(no immunosuppression /

    personalised regenerative medicine)

    • Easy accessibility (minimally-invasive isolation)

    • Ethical acceptance

    The „ideal“ StemCellforRegenerative Medicine

    The “holy Grail” of Stem Cell Research

  • Kaltschmidt, Kaltschmidt and Widera, Stem Cell Rev, 2012

    Neural Crest-Derived Stem Cells (NCSCs)

  • Developmental Potential of Stem Cells

    Modified from Hochedlinger et al

  • Sources of Cranial NCSCs

    Kaltschmidt, Kaltschmidt and Widera, Stem Cell Rev, 2012

  • Sources of Cranial NCSCs

    Kaltschmidt, Kaltschmidt and Widera, Stem Cell Rev, 2012

  • Sources of Cranial NCSCs

  • Sources of Cranial NCSCs

  • Nestin

    NCSCs PerfomSelf-Renewal

    b-III-tubulin: ectoderm

    aSMA: mesoderm

    + 10% FCS

    Hauser et al., Stem Cells Dev, 2012; Greiner et al. Eur Cells Mater, 2011

  • Nestin

    NCSCs DifferentiateintoMesenchymal NeuralCrestDerivatives

    Hauser et al., Stem Cells Dev, 2012; Greiner et al. Eur Cells Mater, 2011

    + Dexamethasone

    + b-glycerophosphate

    + L-ascorbic acid-2-phosphate

  • Nestin

    Hauser et al., Stem Cells Dev, 2012; Greiner et al. Eur Cells Mater, 2011

    pellet culture

    + TGF-b1

    + Dexamethasone

    + ITS-supplement

    NCSCs DifferentiateintoMesenchymalNeuralCrestDerivatives

  • Nestin

    Hauser et al., Stem Cells Dev, 2012; Greiner et al. Eur Cells Mater, 2011

    + IBMX

    + Dexamethasone

    + Indomethacin

    + Insulin

    NCSCs DifferentiateintoMesenchymalNeuralCrestDerivatives

  • Nestin

    Hauser et al., Stem Cells Dev, 2012; Greiner et al. Eur Cells Mater, 2011

    + Low density culture

    + 10 % FCS

    NCSCs DifferentiateintoMesenchymalNeuralCrestDerivatives

  • b-III-tubulin / NF200 / DNA b-III-tubulin / MAP2 / DNA

    Directed Neuronal Differentiation of NCSCs

    Mueller et al. Stem Cells Translational Medicine, 2015

  • Vesicle recycling Calcium Imaging

    low

    [Ca2

    +]

    hig

    h

    Directed Neuronal Differentiation of NCSCs

    Mueller et al. Stem Cells Translational Medicine, 2015

  • Dopaminergic Differentiation of NCSCs in vitro

    TH/DNA21d

    J. Müller et al. Stem Cells Translational Medicine, 2015

  • Injection of 6-OHDA into the MFB leads to loss of TH+ dopaminergic neurons within

    the Substantia nigra

    Substantia nigra Striatum

    Transplantation ofNCSCs intothe6-OHDA Rat Model ofParkinson'sDisease

    Substantia nigra

    6-OHDA

    J. Müller et al. Stem Cells Translational Medicine, 2015

  • Injection of 6-OHDA into the MFB leads to loss of dopaminergic neurons within the

    Substantia nigra

    Substantia nigra Striatum

    SHH/FGF-8

    undifferentiated ITSCs

    Substantia nigra Striatum

    Transplantation of ITSCs 4 weeks post-lesion

    Transplantation ofNCSCs intothe6-OHDA Rat Model ofParkinson'sDisease

    6-OHDA

    J. Müller et al. Stem Cells Translational Medicine, 2015

  • J. Müller et al. Stem Cells Translational Medicine, 2015

    Transplantation ofNCSCs intothe6-OHDA Rat Model ofParkinson'sDisease

  • Transplantation ofNCSCs intothe6-OHDA Rat Model ofParkinson'sDisease

  • E

    F

    A, B: Corpus callosum

    C, D, E: midbrain

    F: Locus caeruleus

    Transplantation ofNCSCs intothe6-OHDA Rat Model ofParkinson'sDisease

    J. Müller et al. Stem Cells Translational Medicine, 2015

  • Osteogenic Differentiation of NCSCs by NanotopologicalCues

    30 nm 100 nm

  • 30 nm 100 nm

    Osteogenic Differentiation of NCSCs by NanotopologicalCues

  • Osteogenic Differentiation of NCSCs by NanotopologicalCues

    Schürmann et al., Stem Cell Research, 2014

  • Osteogenic Differentiation of NCSCs by NanotopologicalCues

    Schürmann et al., Stem Cell Research, 2014

  • Osteogenic Differentiation of NCSCs by NanotopologicalCues

    Schürmann et al., Stem Cell Research, 2014

  • 3D Animal Serum-Free Culture of human NCSCs

  • 3D Animal Serum-Free Culture of human NCSCs

  • 3D Animal Serum-Free Culture of human NCSCs

  • 3D Animal Serum-Free Culture of human NCSCs

    Greiner et al. Eur Cells Mater, 2011

  • 3D Animal Serum-Free Culture of human NCSCs

    Greiner et al. Eur Cells Mater, 2011

  • 3D Animal Serum-Free Culture of human NCSCs

  • Plasticity of Adult Human Neural Crest-Derived Stem Cells

    Summary

    • Human craniofacial tissues contain postmigratory adult NCSCs

    • NCSCs can generate forebrain-like and dopaminergic neurons

    • Transplantation of human NCSCs has beneficial effects in rat model of Parkinson`s disease

    • Human NCSCs give rise to bone cells after cultivation of nanotopologically modified titanium surface

    • NCSCs can be efficiently cultivated in animal serum-free 3D cell culture system

  • Funding

    Stem Cell Biology and Regenerative Medicine GroupSchool of Pharmacy

    University of Reading, United Kingdom