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
Falconieri A., Da Palmata L., Cappello V., Schmidt T.J.N., Folino P., Storti B., Bizzarri R., Raffa V. The Extremely Low Mechanical Force Generated by Nano-Pulling Induces Global Changes in the Microtubule Network, Nuclear Morphology, and Chromatin Transcription in Neurons. (2025) Small, DOI: 10.1002/smll.202503011
Falconieri A., Coppini A., Raffa V. Microtubules as a signal hub for axon growth in response to mechanical force (2024) Biological Chemistry, 405 (1), pp. 67 – 77 DOI: 10.1515/hsz-2023-0173
Merighi F., De Vincentiis S., Onorati M., Raffa V. Long-term Mouse Spinal Cord Organotypic Slice Culture as a Platform for Validating Cell Transplantation in Spinal Cord Injury (2024) Journal of Visualized Experiments , 2024 (206), art. no. e66704 DOI: 10.3791/66704
Falconieri A., Folino P., Da Palmata L., Raffa V. Nano-pulling stimulates axon regeneration in dorsal root ganglia by inducing stabilization of axonal microtubules and activation of local translation (2024) Frontiers in Molecular Neuroscience, 17, art. no. 1340958 DOI: 10.3389/fnmol.2024.1340958
Falconieri A., De Vincentiis S., Cappello V., Convertino D., Das R., Ghignoli S., Figoli S., Luin S., Català-Castro F., Marchetti L., Borello U., Krieg M., Raffa V. Axonal plasticity in response to active forces generated through magnetic nano-pulling (2023) Cell Reports, 42 (1), art. no. 111912. DOI: 10.1016/j.celrep.2022.111912
De Vincentiis S., Baggiani M., Merighi F., Cappello V., Lopane J., Di Caprio M., Costa M., Mainardi M., Onorati M., Raffa V. Low Forces Push the Maturation of Neural Precursors into Neurons (2023) Small, 19 (30), art. no. 2205871. DOI: 10.1002/smll.202205871
Raffa, V. Force: A messenger of axon outgrowth (2022) Seminars in Cell and Developmental Biology, DOI: 10.1016/j.semcdb.2022.07.004