Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology,...
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Transcript of Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology,...
Research on stem cells: Ideas, questions, data gathering
Brenda Russell PhDPhysiology, Bioengineering, Medicine
UIC
22 Feb, 2008
BIG QUESTION ? How is life evolved to adapt to physical forces?
Idea = guess= hypothesisBased on
work done by others and new unexpected observations
Scientific method Tests to see if guesses are correct
or not
Hypothesis = ?
Strong attachment of cells to surroundings affects their function
Test
Alter surroundings with bioengineering and observe cells
Stem cell differentiation and maturation
Chemical: growth factors, genes, drugs, cell signaling
Physical: forces, topography, scaffolds
stem finalCell source
Cell soon after plating in culture
Focal adhesions
www.courses.rochester.edu
Crawling
flat 10 m high
100
200
300
fib
rob
las
t #
x 1
00
0
Day 1 2 5 1 2 5 Flat Micropeg
Fibroblasts on 2D flat or 3D niche membranes
Boateng, SY, TJ Hartman, N Ahluwalia, H Vidula, TA. Desai and B. Russell. Am J. Physiol: Cell. 285:C171-C182, 2003
Net force is zero
Cells can do physics
Newton’s Third Law of PhysicsEvery force has an equal and opposite reactive force.
N
How many cell divisions before cells specialize?
One division = 2 cells
Two divisions = 4 cells
Three divisions = 8 cells
Four divisions = 16 cells
One cell is now in the middleRest have inner and outer surfaces
Physical Niche
Engler AJ, Sen S, Sweeney HL, Discher DE.Matrix elasticity directs stem cell lineage specification.Cell. 2006 Aug 25;126(4):677-89.
brain muscle bone
Hypothesis
Stem cells respond to the physical cues
Experiment to test
Alter niche by microtopography and measure cell response
P
P
Projection
cardiac myocyte
non Myocyte
Microtopography: mouse cardiac stem cells
Disclosure: Microtextured surfaces will be manufactured by Cell Habitats, LLCUS Patent: Russell and Desai [email protected] ©
*
*
* p<0.05
(4 days)
Mouse embryonic stem cell proliferation
0
0.2
0.4
0.6
0.8
1
1.2
1
Projection Spacing (n=4)
Rat
io o
f F
lat
80um
500um
Mouse embryonic stem cells division is blunted by 80um projections
0
0.1
0.2
0.3
0.4
0.5
near far
Distance from Projection
Rat
io d
ivid
ing
Beating cells derived from mouse embryonic stem cellsFlat surface
Beating cells grown on microprojections
Conclusion• Microtopgraphy blunts proliferation of stem
cells
• Beating rates of derived heart cells vary greatly when plated on microprojections
Sciencenew ideasquestions test with latest techniques measurments
Leads to next guess and next ?
AcknowledgementsFunding from NIH and Illinois regenerative medicine
Russell Lab UIC
Sam Boateng PhDDelara Motlagh PhDHaytham Mansour PhDYevgeniya Koshman PhD Sam SenyoJesse BiehlJohn Collins
Tejal Desai, Ph.D.Bioengineering, UCSF
Allen Samarel MDLoyola, Maywood, IL