WingforLife 2021

STRETCH-GROWTH AND CELL THERAPY: A NOVEL COMBINATORIAL APPROACH FOR TREATING SPINAL CORD INJURIES

In spinal cord injury (SCI), the stimulation of the axonal regeneration of the injured resident neurons represents a big challenge. The transplantation of neural precursor cells (NPCs) has been also proposed to replace lost or injured neurons but the efficiency of their spontaneous maturation into mature neurons and integration into the existing spinal milieu is often sub-optimal. Recently, our team has demonstrated that the application of extremely low mechanical forces strongly stimulates axonal out-growth and maturation of  neurons and NPCs. However, the use of mechanical forces, alone or in combination with other approaches, to accelerate the regeneration process in vivo has been never investigated because of the lack of enabling technologies. Recently, we developed a new nanotechnology-based tool for stretching axons in vivo. Specifically, our team demonstrated that magnetic nanoparticles can be uptaken by neurons with no damage, thus making these cells responsive to the application of external magnetic fields. The ensuing extremely low mechanical force dramatically stimulates axon elongation and neuron maturation. Our idea is to stretch the resident injured axons for stimulating them to elongate and to cross the lesion gap. Simultaneously, we would also stretch NPCs – transplanted into the lesion site – in order to propel their differentiation into a neuronal lineage, thereby bridging or circumventing the lesion area, by creating a relay circuit. We hope that this combinatorial approach will stimulate the regeneration of damaged spinal cord circuits to enhance recovery of limb function in SCI models

MAIN COLLABORATIONS

Marco Onorati, UNIPI, IT

Marco Mainardi, CNR; IT

Mario Costa, CNR, IT

PUBLICATIONS

Raffa, V. Force: A messenger of axon outgrowth (2022) Seminars in Cell and Developmental Biology, DOI: 10.1016/j.semcdb.2022.07.004