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Project Plans

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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Project Plans

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  1. Sydney Geissler Schmidt lab September 14, 2011 Project Plans

  2. 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

  3. Spinal Cord Injury • Available treatments are palliative and preventative. http://www.articleslounge.com/medical/spinal-cord-injury-sci/

  4. 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/

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. Hyaluronic Acid • Extracellular matrix GAG • Hydrophilic • Non cell adhesive

  12. 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

  13. Spinal Progenitor Cells in 3D Matrix • 3D expansion • Directed differentiation

  14. 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.

  15. 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.

  16. Gel Types

  17. Mechanical Properties • The difference in compressive modulus of the gels could contribute to the difference in differentiation within the gels • HA mediates compressive modulus

  18. 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

  19. 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.

  20. Spinal Progenitor Differentiation Within Gels • Collagen gels promote differentiation into astrocytes (a), while col/HA/Ln gels promote neuronal differentiation (b).

  21. 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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