ILANIT 2020

Engineering fully human motor neuron implants for treating the injured spinal cord


Lior Wertheim 1,3 Yona Goldshmit 2 Reuven Edri 1 Tal Dvir 1,3,4,5
1Department of Molecular Microbiology and Biotechnology, Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Science, Tel Aviv University, Tel Aviv, Israel, Iceland
2Sackler School of Medicine, Steyer School of Health Professions, Sackler School of Medicine, Tel-Aviv University, P.o. Box 39040, Tel Aviv 6997801, Israel
3Department of Materials Science and Engineering, Department of Materials Science and Engineering, Tel Aviv University, Tel Aviv, Israel
4Center for Nanoscience and Nanotechnology, Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, Israel
5Sagol Center for Regenerative Biotechnology, Sagol Center for Regenerative Biotechnology, Tel Aviv University, Tel Aviv, Israel

Spinal cord injury (SCI) disrupts signals between the brain and the body. In traumatic SCI, the primary impact damages cells and initiates a complex secondary injury cascade, which cyclically produces the death of neurons and glial cells, leading to ischemia and inflammation. In our approach, a small piece of fatty tissue biopsy is extracted from patients and the cellular and a-cellular materials are separated. While the cells are reprogrammed to become iPSCs, the extracellular matrix is processed to become a personalized hydrogel. Here, after mixture of the cells and the hydrogel, efficient differentiation into spinal cord motor-neuronal networks was performed to engineer patient-specific spinal cord implants. The implants were characterized for morphology and function and then transplanted into injured mice. Histologically, implant treated mice exhibited reduced inflammation and glial scar formation alongside high axonal recovery in the lesion area. Moreover, quantitative behavioral assessments were performed using catwalk system for gait analysis. The degree of inter-limb coordination during the gait cycle, measured by the regulatory index, was significantly improved in implant treated mice.









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