Dr Darius Widera Lecturer (Assistant Professor) in Stem Cell Biology...
Transcript of Dr Darius Widera Lecturer (Assistant Professor) in Stem Cell Biology...
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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
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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
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What are Stem Cells?
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The Promise of Stem Cell Research
The Fountain of Youth, 1546 painting by Lucas Cranach the Elder
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Stem Cells: Mysterious Cure for any and every disease?
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The Aim of Stem Cell Research
Modified from NIH Stem Cell Info
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Developmental Potential of Stem Cells
Modified from Hochedlinger et al
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• 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
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Kaltschmidt, Kaltschmidt and Widera, Stem Cell Rev, 2012
Neural Crest-Derived Stem Cells (NCSCs)
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Developmental Potential of Stem Cells
Modified from Hochedlinger et al
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Sources of Cranial NCSCs
Kaltschmidt, Kaltschmidt and Widera, Stem Cell Rev, 2012
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Sources of Cranial NCSCs
Kaltschmidt, Kaltschmidt and Widera, Stem Cell Rev, 2012
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Sources of Cranial NCSCs
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Sources of Cranial NCSCs
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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
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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
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Nestin
Hauser et al., Stem Cells Dev, 2012; Greiner et al. Eur Cells Mater, 2011
pellet culture
+ TGF-b1
+ Dexamethasone
+ ITS-supplement
NCSCs DifferentiateintoMesenchymalNeuralCrestDerivatives
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Nestin
Hauser et al., Stem Cells Dev, 2012; Greiner et al. Eur Cells Mater, 2011
+ IBMX
+ Dexamethasone
+ Indomethacin
+ Insulin
NCSCs DifferentiateintoMesenchymalNeuralCrestDerivatives
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Nestin
Hauser et al., Stem Cells Dev, 2012; Greiner et al. Eur Cells Mater, 2011
+ Low density culture
+ 10 % FCS
NCSCs DifferentiateintoMesenchymalNeuralCrestDerivatives
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b-III-tubulin / NF200 / DNA b-III-tubulin / MAP2 / DNA
Directed Neuronal Differentiation of NCSCs
Mueller et al. Stem Cells Translational Medicine, 2015
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Vesicle recycling Calcium Imaging
low
[Ca2
+]
hig
h
Directed Neuronal Differentiation of NCSCs
Mueller et al. Stem Cells Translational Medicine, 2015
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Dopaminergic Differentiation of NCSCs in vitro
TH/DNA21d
J. Müller et al. Stem Cells Translational Medicine, 2015
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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
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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
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J. Müller et al. Stem Cells Translational Medicine, 2015
Transplantation ofNCSCs intothe6-OHDA Rat Model ofParkinson'sDisease
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Transplantation ofNCSCs intothe6-OHDA Rat Model ofParkinson'sDisease
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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
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Osteogenic Differentiation of NCSCs by NanotopologicalCues
30 nm 100 nm
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30 nm 100 nm
Osteogenic Differentiation of NCSCs by NanotopologicalCues
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Osteogenic Differentiation of NCSCs by NanotopologicalCues
Schürmann et al., Stem Cell Research, 2014
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Osteogenic Differentiation of NCSCs by NanotopologicalCues
Schürmann et al., Stem Cell Research, 2014
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Osteogenic Differentiation of NCSCs by NanotopologicalCues
Schürmann et al., Stem Cell Research, 2014
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3D Animal Serum-Free Culture of human NCSCs
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3D Animal Serum-Free Culture of human NCSCs
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3D Animal Serum-Free Culture of human NCSCs
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3D Animal Serum-Free Culture of human NCSCs
Greiner et al. Eur Cells Mater, 2011
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3D Animal Serum-Free Culture of human NCSCs
Greiner et al. Eur Cells Mater, 2011
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3D Animal Serum-Free Culture of human NCSCs
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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
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Funding
Stem Cell Biology and Regenerative Medicine GroupSchool of Pharmacy
University of Reading, United Kingdom