Sydney geissler schmidt lab september 14 2011
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Sydney Geissler Schmidt lab September 14, 2011. Project Plans. Spinal Cord Injury. 200,000 people in the US suffer from paralysis due to spinal cord injury. More than half of spinal cord injuries are sustained by people between the ages of 15 and 29.

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Sydney Geissler

Schmidt lab

September 14, 2011

Project Plans


Spinal Cord Injury

  • 200,000 people in the US suffer from paralysis due to spinal cord injury.

  • More than half of spinal cord injuries are sustained by people between the ages of 15 and 29.

  • 60% of spinal cord injuries are cervical injuries.

http://sporthealthcare.com/compression-of-the-spinal-cord.html


Spinal Cord Injury

  • Available treatments are palliative and preventative.

http://www.articleslounge.com/medical/spinal-cord-injury-sci/


Current Research

  • Decrease axon dieback

  • Decrease scar formation

  • Encourage regeneration

http://stemcellumbilicalcordblood.com/stem-cell-information/stem-cell-research/stemcyte-conducting-stem-cell-clinical-trials-for-spinal-cord-injuries/


Current Research

  • Decrease axon dieback

  • Decrease scar formation

  • Encourage regeneration

The Extracellular Matrix Glycoprotein Tenascin-C Is Beneficial for Spinal Cord Regeneration

Jian Chen et al. Molecular Therapy 2010


Current Research

  • Decrease axon dieback

  • Decrease scar formation

  • Encourage regeneration

Wanner, I. B., et al. (2008). A new in vitro model of the glial scar inhibits axon growth. Glia 56, 1691–1709.


Current Research

  • Decrease axon dieback

  • Decrease scar formation

  • Encourage regeneration

PTEN deletion enhances the regenerative ability of adult corticospinal neurons

Liu et al. Nature Neuroscience, 2010


Spinal Progenitor Implantation

  • Neural Progenitor cells prevent axonal dieback in dorsal column crush injury

Multipotent Adult Progenitor Cells Prevent Macrophage-Mediated Axonal Dieback and Promote Regrowth after Spinal Cord Injury

Sarah A. Busch, Jason A. Hamilton, Kevin P. Horn, Fernando X. Cuascut, Rochelle Cutrone, Nicholas Lehman, Robert J. Deans, Anthony E. Ting, Robert W. Mays, and Jerry Silver


Spinal Progenitor Implantation

  • SC NPC’s have been implanted into spinal cord for regeneration

  • Found mostly oligodendrocytes

  • Low survival rate

Transplanted adult spinal cord derived neural stem/progenitor cells promote early functional recovery after rat spinal cord injury.

Parr AM, Kulbatski I, Zahir T et al. Neuroscience 2008


Spinal Progenitor Implantation

  • Spinal Progenitor Implantation along with ChABC promotes plasticity and functional recovery

Synergistic Effects of Transplanted Adult Neural Stem/Progenitor Cells, Chondroitinase, and Growth Factors Promote Functional Repair and Plasticity of the Chronically Injured Spinal Cord

SoheilaKarimi-Abdolrezaee, EftekharEftekharpour, Jian Wang, Desiree Schut, and Michael G. Fehlings


Hyaluronic Acid

  • Extracellular matrix GAG

  • Hydrophilic

  • Non cell adhesive


Hyaluronic Acid

  • High molecular weight HA prevents glial scar formation

High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury

Zin Z Khaing, BrianDMilman, Jennifer E Vanscoy, Stephanie K Seidlits, Raymond J Grill and Christine E Schmidt


Spinal Progenitor Cells in 3D Matrix

  • 3D expansion

  • Directed differentiation


Project Plans

Aim 3

In vivo testing of gels for spinal cord regeneration.

Aim 2

Optimization of chemical and mechanical cues for differentiation within gels.

Aim 1

Chemical and mechanical cues for differentiation. Mechanical testing of thermally gelling gels.


Project Plans

Aim 3

In vivo testing of gels for spinal cord regeneration.

Aim 2

Optimization of chemical and mechanical cues for differentiation within gels.

Aim 1

Chemical and mechanical cues for differentiation. Mechanical testing of thermally gelling gels.


Gel Types


Mechanical Properties

  • The difference in compressive modulus of the gels could contribute to the difference in differentiation within the gels

  • HA mediates compressive modulus


Chemical Cues for Differentiation

  • Cannot decouple mechanical and chemical cues

  • Create methacrylated HA gels to control mechanical properties

  • Control concentrations of collagen and laminin within same mechanical property gels

Selective Differentiation of

Neural Progenitor Cells by

High–Epitope Density Nanofibers

Gabriel A. Silva, Catherine Czeisler et al. Science 2004


Project Plans

Aim 3

In vivo testing of gels for spinal cord regeneration.

Aim 2

Optimization of chemical and mechanical cues for differentiation within gels.

Aim 1

Chemical and mechanical cues for differentiation. Mechanical testing of thermally gelling gels.


Spinal Progenitor Differentiation Within Gels

  • Collagen gels promote differentiation into astrocytes (a), while col/HA/Ln gels promote neuronal differentiation (b).


Project Plans

Aim 3

In vivo testing of gels for spinal cord regeneration.

Aim 2

Optimization of chemical and mechanical cues for differentiation within gels.

Aim 1

Chemical and mechanical cues for differentiation. Mechanical testing of thermally gelling gels.


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