Stem Cells and Regenerative Medicine

Outline of Presentation

• What is stem cell research?• What are the different types of stem cells?• Fertilization and embryonic development• What makes stem cells unique?• How do we culture stem cells?• What are examples of future stem cell therapies?• Conclusion and future directions

What is stem cell research?

• Understand more about development, aging, disease– Experimental model systems

• Prevent or treat diseases and injuries– Cell-based therapies– Pharmaceutical development

• Includes testing and drug delivery

Trachea transplantation:Example of stem cell-based tissue regeneration

Outline of Presentation

• What is stem cell research?• What are the different types of stem cells?• Fertilization and embryonic development• What makes stem cells unique?• How do we culture stem cells?• What are examples of future stem cell therapies?• Conclusion and future directions

This cellCan form the

Embryo and placenta

This cellCan form the

embryo

Fully mature

Induced Pluripotent Stem (iPS) CellsGenetically engineering new stem cells

Skin cells iPS cells

Outline of Presentation

• What is stem cell research?• What are the different types of stem cells?• Fertilization and embryonic development• What makes stem cells unique?• How do we culture stem cells?• What are examples of future stem cell therapies?• Conclusion and future directions

In the IVF procedure, sperm and eggs “interact” in a dish leading to insemination.They literally swim up to the egg and burrow toward the nucleus.The first one to get there wins, and all others are blocked out.

Male fertility issue: Sometimes sperm cannot latch onto and penetrate the egg. They may choose to have Intra(within)-Cytoplasmic Sperm Injection (ICSI)

Day 1

Day 1

Day 1

Day 2

Day 2

Day 3

Day 4

EmbryonicStemCells

Day 5

At what point is this a fetus? • Days 7-14: Uterine implantation• Day 14: Three distinct layers begin to form (no

more pluripotent stem cells)• Days 14-21: Beginning of future nervous system• Days 21-24: Beginning of future face, neck,

mouth, and nose• Weeks 3-8: Beginning of organ formation

This picture is Week 5

• Week 5-8+: Now it’s called a fetus (no consensus on a single timepoint)

Embryonic Development: Fish model

Keller et al. 2008

Outline of Presentation

• What is stem cell research?• What are the different types of stem cells?• Fertilization and embryonic development• What makes stem cells unique?• How do we culture stem cells?• What are examples of future stem cell therapies?• Conclusion and future directions

Symmetric cell division

Asymmetric cell division

1. Self-renews 2. Differentiates

Progenitor cell

Stem cell Stem cell

SELF – RENEWAL

DIFFERENTIATION

DIFFERENTIATION

Outline of Presentation

• What is stem cell research?• What are the different types of stem cells?• Fertilization and embryonic development• What makes stem cells unique?• How do we culture stem cells?• What are examples of future stem cell therapies?• Conclusion and future directions

Signals to Stem Cells

Other Cells

Matrix Molecules

Self-Renewal

Soluble Factors

Differentiation

Little, et al. Chemical Reviews (2008).

Embryonic stem cells in the dish:How do we culture ES cells?

Culture methods

Yellow

pH 6.8 – slightly acidic 8.4 – slightly basic

Red

7.0 - Neutral

Fluorescent imaging of embryonicstem cell colonies.

Outline of Presentation

• What is stem cell research?• What are the different types of stem cells?• Fertilization and embryonic development• What makes stem cells unique?• How do we culture stem cells?• What are examples of future stem cell therapies?• Conclusion and future directions

Spinal cord injury:Example of embryonic stem cell-based therapy

Geron video: http://www.geron.com/grnopc1clearance/

Stem cells for drug deliveryMore focused delivery, fewer side affects

NSCs injected

(no tumor)

NSCs injected (tumor)

Day 0 Day 7 Day 14

Shah et al. Dev Neurosci 2004

Outline of Presentation

• What is stem cell research?• What are the different types of stem cells?• Fertilization and embryonic development• What makes stem cells unique?• How do we culture stem cells?• What are examples of future stem cell therapies?• Conclusion and future directions

Why do researchers want to use embryonic stem cells along with other technologies?• Pluripotent

– Expanded developmental potential allows them to be used in ways that adult stem cells cannot

• Can proliferate indefinitely in culture• Easier to obtain than adult stem cells

Science is discovering the unknown

• Stem cell field is still in its infancy• Human embryonic stem cell research is a decade old,

adult stem cell research has 30-year head start• Holds hope for curing or improving treatments for

70+ diseases

How can you help to shape the direction of this field?

Students: https://www.surveymonkey.com/s/stemcell2010  

Teacher: https://www.surveymonkey.com/s/stemcellteach2010

Take our survey please!

If enough time!

• Continue on to talk about chemical engineering.

Chemical engineering• Cells can be grown in 2D

• Some chemical engineers find new surfaces to grow cells on/in that promote proliferation or differentiation

or 3D

Interpenetrating Polymer Network

Saha, K et al. J Biomed Mater Res A. (2007)Harbers, G. M., et. al. Langmuir. (2005)Bearinger, JP et al., J. Biomat. Sci. Polym. Ed. (1998)

NH

O

NH

O

Free radical polymerization

NNH

O

H

OHO

O

OO

O1000

Free radical polymerization

H2NO NH2

3400 N O N

O

O O

O

N aO3SO

Acetyl-CGGNGEPRGDTYRAY-NH2Bsp-RGD (15)

Bacterium

Selecting for adhesion molecules

• Grow Bacteria having adhesion molecules + stem cells

• Wash away non-adherent bacteria

• Identify the molecules that stuck

Bacterium

BacteriumBacterium

Bacterium

Stem Cell

H2NO NH2

3400 N O N

O

O O

O

N aO3SO

NH

O

NH

O

Free radical polymerization

NNH

O

H

OHO

O

OO

O1000

Free radical polymerization

Stem cell Stem cell