טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentShor Erez
SubjectEngineered Pre-Vascularized Nerve Transplant for the
Treatment of Spinal Cord Injury
DepartmentDepartment of Biomedical Engineering
Supervisors Professor Shulamit Levenberg
Professor Shy Shoham


Abstract

Spinal cord injury is a devastating medical condition. Recent developments in pre-clinical and clinical research have started to yield neural implants inducing functional recovery after spinal cord transection injury. We developed a 3D construct bearing human oral mucosa stem cells (hOMSC) induced to secrete neuroprotective, immunomodulatory and regeneration-associated factors in a complete spinal cord transection rat model. Implantation of this construct yielded significant functional recovery. Imaging and electrophysiological assessments confirmed a functional reconnection bridging the injured area. An increased number of myelinated axons and neural precursors, alongside less glial scar tissue were histologically observed.

To study cell dynamics and cellular level therapy response we developed neurophotonic tools coupled with optogenetic methods to investigate cell morphology and activity characteristics of neural implants over time in the cellular level. These methods were developed to support in-vitro and in-vivo experiments of a mouse spinal cord injury model.

We utilized these method to investigate the functional properties of an engineered pre-vascularized neural implant. Vascularization plays an important role improving integration of engineered tissue. The interplay between vascular and neural networks renders vascularization even more important in this case as it also modulates the morphology and activity patterns of the neurons implanted. We compared between vascularized and non-vascularized constructs and presented richer, more complex morphology and activity patterns of vascularized constructs. This work enables further optimization of neural implants. It also provides valuable tools to monitor and investigate the behavior of implants designed for various neurological disorders in the cellular level over time.