Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology,...

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Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 [email protected] ©

Transcript of Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology,...

Page 1: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Research on stem cells: Ideas, questions, data gathering

Brenda Russell PhDPhysiology, Bioengineering, Medicine

UIC

22 Feb, 2008

[email protected] ©

Page 2: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

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

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Page 3: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Hypothesis = ?

Strong attachment of cells to surroundings affects their function

Test

Alter surroundings with bioengineering and observe cells

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Page 4: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Stem cell differentiation and maturation

Chemical: growth factors, genes, drugs, cell signaling

Physical: forces, topography, scaffolds

stem finalCell source

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Page 5: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Cell soon after plating in culture

Focal adhesions

www.courses.rochester.edu

Crawling

Page 6: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Micro Soccer

reactive forces

immobilesphere

mobilesphere

reactive forces

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Page 7: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

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

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Page 8: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Net force is zero

Cells can do physics

Newton’s Third Law of PhysicsEvery force has an equal and opposite reactive force.

N

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Page 9: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Hypothesis

Stem cell niche ofmicroenvironment affects function

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Page 10: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

How many cell divisions before cells specialize?

One division = 2 cells

Two divisions = 4 cells

Three divisions = 8 cells

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Page 11: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Four divisions = 16 cells

One cell is now in the middleRest have inner and outer surfaces

Physical Niche

Page 12: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

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

Page 13: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Hypothesis

Stem cells respond to the physical cues

Experiment to test

Alter niche by microtopography and measure cell response

Page 14: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

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] ©

Page 15: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Cell division on flat surfaces

Dividing

Green- BrDU+ALL: Red- PI

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Page 16: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Cell division blunted by 80µm projections

DividingGreen- BrDU+

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Page 17: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

*

*

* 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

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Page 18: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

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

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Page 19: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Beating cells derived from mouse embryonic stem cellsFlat surface

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Page 20: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Beating cells grown on microprojections

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Page 21: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Conclusion• Microtopgraphy blunts proliferation of stem

cells

• Beating rates of derived heart cells vary greatly when plated on microprojections

Page 22: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

Sciencenew ideasquestions test with latest techniques measurments

Leads to next guess and next ?

Page 23: Research on stem cells: Ideas, questions, data gathering Brenda Russell PhD Physiology, Bioengineering, Medicine UIC 22 Feb, 2008 Russell@uic.edu ©

AcknowledgementsFunding from NIH and Illinois regenerative medicine

Russell Lab UIC

Sam Boateng PhDDelara Motlagh PhDHaytham Mansour PhDYevgeniya Koshman PhD Sam SenyoJesse BiehlJohn Collins

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Tejal Desai, Ph.D.Bioengineering, UCSF

Allen Samarel MDLoyola, Maywood, IL