Thesis Title: Study of combinatorial cell therapy and neuroprotective agents for the treatment of spinal cord injury in experimental models

Author: Pablo Bonilla Villamil

PhD. Supervisors: Victoria Moreno Manzano, Esther Giraldo Reboloso

Tribunal: Enrique Lanuza (UV, Valencia), Guillermo García Alias (UAM, Barcelona), Marc Oria (Children Hospital, Cincinnati, USA)

Summary:

Traumatic spinal cord injury (SCI) is a devastating and debilitating neurological disorder characterized by a variable degree of permanent motor, sensory and/or autonomic dysfunction. Neural stem cell (NSC) transplantation offers a promising therapeutic tool for SCI by providing neuroprotection and neuroregeneration. However, the environment following spinal cord injury limits the therapeutic potential of cell therapies by resulting in poor cell survival and engraftment and inadequate differentiation, and to date, cell therapies have shown limited functional recovery in clinical trials. Therefore, the use of combinatorial therapies has been postulated to overcome these limitations and enhance the therapeutic benefits of cell therapies following SCI. Pablo Bonilla´s PhD thesis evaluated different translational strategies with the aim of improving and enhancing the effect of NSCs transplantation to rescue neuronal function after SCI by 1) a combination therapy of human neural stem cells derived from induced pluripotent stem cells (iPSC-NSCs), mesenchymal stem cells (MSCs) and a curcumin nanoconjugate (PA-C); 2) a novel strategy for transplantation of iPSC-NSCs combined with PA-C using a demilunar hyaluronic acid scaffold, for a minimally invasive transplantation strategy; and 3) transplantation of human fetal neural progenitors (hfNPCs) conditioned with the conjugated form of the Rho/Rock inhibitor fasudil (PGA-SS-FAS).