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

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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Hypothesis = ?

Strong attachment of cells to surroundings affects their function

Test

Alter surroundings with bioengineering and observe cells

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Stem cell differentiation and maturation

Chemical: growth factors, genes, drugs, cell signaling

Physical: forces, topography, scaffolds

stem finalCell source

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Cell soon after plating in culture

Focal adhesions

www.courses.rochester.edu

Crawling

Micro Soccer

reactive forces

immobilesphere

mobilesphere

reactive forces

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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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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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Hypothesis

Stem cell niche ofmicroenvironment affects function

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How many cell divisions before cells specialize?

One division = 2 cells

Two divisions = 4 cells

Three divisions = 8 cells

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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 Russell@uic.edu ©

Cell division on flat surfaces

Dividing

Green- BrDU+ALL: Red- PI

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Cell division blunted by 80µm projections

DividingGreen- BrDU+

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*

*

* 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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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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Beating cells derived from mouse embryonic stem cellsFlat surface

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Beating cells grown on microprojections

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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

Russell@uic.edu

Tejal Desai, Ph.D.Bioengineering, UCSF

Allen Samarel MDLoyola, Maywood, IL