Embryonic stem cells (ESCs) can form any cell in the body. This also means that they have the potential to form tumors. Human neural stem cells (hNSCs) are a specialized subset of stem cells which can only form cells of the nervous system (neurons, oligodendrocytes, and astrocytes), and are thus safer for use as a therapeutic. hNSCs can be derived from embryonic, fetal, or adult (iPS) sources. My lab is interested in understanding how different methods of deriving and culturing hNSCs affect their ability to proliferate and differentiate in vitro and respond to the injured microenvironment in vivo, with the goal of treating neurotrauma (spinal cord injury and traumatic brain injury).
Different Sources of hNSCs
Do hNSCs from embryonic, fetal, and/or adult sources have different properties? Is one cell line or one source better at making new neurons than another? In collaboration with the Anderson Lab, we are comparing hNSCs from multiple sources in models of neurotrauma (spinal cord injury – SCI and traumatic brain injury – TBI).
Transplantation of hNSCs in Spinal Cord Injured Mice and Traumatic Brain Injury
Neurotramua causes loss of neurons, oligodendrocytes, and/or astrocytes. Neurons send signals from one part of the brain to another and/or tell muscles to move. Oligodendrocytes insulate neural signals by surrounding axons. If we can replace these lost cells via hNSCs, we may be able to restore function after injury. Methods include testing animal behavior and quantification of surviving human cells, followed by microscopy and stereology to identify cell fate and quantify cell engraftment, coupled with electron microscopy to visualize integration with the host.
Immunosuppressants & hNSCs
The therapeutic use of hNSCs in neurotrauma will require immunosuppressants to protect the transplant from the host’s immune response. Do these drugs affect hNSC proliferation, migration and/or fate? How can we maximize human cell survival when injected into the foreign immune environment of an animal model?
Time-lapse imaging of Stem cell proliferation migration, and fate
One mechanism for the therapeutic potential of stem cells is due to their differentiation potential. To enable cell transplantation therapies to be realized, we need to understand how individual stem cells choose what type of cell to be, in other words, how they choose their fate. Time-lapse imaging can track cell lineage and fate over days or weeks in vitro, revealing individual cell responses to inflammatory cues, differentiation factors, and/or drug treatments.
Controlled Release Scaffolds for Nerve Regeneration
Injury to the spinal cord results in paralysis below the level of the injury, limited regeneration occurs as result of the local environment, which is deficient in stimulatory factors and has an excess of inhibitory factors. We are trying to develop multi-functional biomaterials that bridge the injury site to control the microenvironment. Such materials promote and direct axonal growth into and through and bridge, and enhance axonal re-entry into the host tissue to form functional connections with intact circuitry. In collaboration with Lonnie Shea (Northwestern University) we have developed multiple channel bridges that mechanically stabilize the injury site to limit secondary damage, and promote axonal growth into and across the injury, with axonal re-entry into the host tissue.