Vittoria Raffa and Marco Mainardi, Department of Biology, Università Di Pisa, Pisa, Italy

Stretch-growth and cell therapy: a novel combinatorial approach

Funded in: 2021, 2022, 2023

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Problem: Axonal regeneration represents a big challenge
Target: Axonal out-growth, maturation of neurons and NPCs
Goal: Combinatorial approach to stimulate regeneration

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 also been 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, the research group 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 never been investigated because of the lack of enabling technologies.

They developed a new nanotechnology-based tool for stretching axons in vivo. Specifically, the 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. Their idea is to stretch the resident injured axons for stimulating them to elongate and to cross the lesion gap.

Simultaneously, the scientists would also stretch NPCs that were transplanted into the lesion site. That should lead to their differentiation into a neuronal lineage, thereby bridging or circumventing the lesion area, by creating a relay circuit. They hope that this combinatorial approach will stimulate the regeneration of damaged spinal cord circuits to enhance recovery of limb function in SCI models.