Giles Plant Lab Research
Our Research Mission
A compelling question in the field of SCI research is: if severed axons can be regrown just beyond the lesion site, how much functional benefit does this realistically offer a SCI patient? There have been several efforts to correlate the return of function with new axonal growth, but many have left unanswered the question of whether these axons re-establish appropriate functional connections between the deactivated cortical motor neurons and the limbs they once innervated. In addition, these therapeutics are not typically constrained to a specific neuron or fiber population, it remains unknown if there are variables secondary to our treatments that could instead be directly manipulated to more effectively induce functional recovery.
Major Research Focus Areas of the Laboratory
Capacity of intraspinal and intravenous mesenchymal stem cells to improve functional outcomes in cervical SCI models in rats and mice
Multipotent precursor cells (MPCs) or mesenchymal cells (MSCs) routinely taken from the stromal tissue of bone marrow have gained widespread support in therapeutic application in SCI for the promotion of tissue sparing, axon regeneration and functional recovery.
We are researching optimal delivery methods for highly purified mesenchymal cells isolated from the mouse or human, in order to improve cervical SCI behavioral and functional outcomes. We deliver the cells via two routes: either directly into the spinal cord, or via intravenous delivery. Analysis includes the acute versus chronic delivery of the cells, non invasive bioluminescent imaging to track the cells in vivo, anatomical evaluation of therapy, behavioral assessments and immunological assessments using in vitro and in vivo modeling.
Efficacy of human induced pluripotent stem cell (hiPS) lines to improve functional outcomes in cervical SCI.
We are investigating the efficacy of human iPS lines differentiated into neuronal transplants to form relay/bridging grafts after acute SCI in the cervical spinal cord. Within these studies we are exploring the ability of these neurons, in conjunction with intensive rehabilitation, to induce long tract growth, synapse formation to the host spinal cord, and overall improve functional recovery.
Mechanisms of olfactory ensheathing cells to stimulate CNS regeneration
Olfactory ensheathing cells (OEC) are a type of glial cell that has been found to have anatomical and functional efficacy when transplanted to SCI injured mammals. However, little is known of the OEC mechanisms of action either in axonal regeneration of myelination. OECs can be isolated from peripheral and central locations within the olfactory system and also from different stages of development and adult. OEC at stages of development vary in the axonal regenerative and myelination capabilities. We have successfully isolated OEC specific genes that we postulate to have key roles in CNS regenerative repair. This research involves the use of in vitro co-cultures and in vivo transplantation models. Additional techniques involve gene therapy and conditional transgenic mice.
Biomimetic implants for spinal cord injury
Cellular transplantation as a means to repair the spinal cord is a well established field of research, with numerous cell types being investigated. Cells such as Schwann cells, olfactory glia, stem cells, mesenchymal cells, precursors and iPS have all been used with some success. However, cell survival is very low due to losses via immunological mechanisms and also “anoikis”.
Cells within the body have well defined niches, providing key support for their integration, survival and function. For this reason we are exploring the use of self-assembling peptide gels (in collaboration with Dr Sarah Heilshorn) to transplant (glial and stem cells) into the injured spinal cord.
These peptide gels can be used as an injectable material directly into the lesion area, to provide surfaces for the cells to attach and also protect cells from immediate immune attack. These peptide solutions, once injected, form soft porous gels without the need for pH or temperature changes to cross link the gels. This provides a very stable non toxic gel for transplantation.