Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord
| Autor: | José Manuel García-Verdugo, Clara Alfaro-Cervello, Melania Cusimano, Giuliana Salani, Matteo Donegà, Daniela Biziato, Stefano Pluchino, Michele De Palma, Gianvito Martino, Giancarlo Comi, Elena Brambilla, Ferdinando Pucci, Silvia Snider |
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| Přispěvatelé: | Cusimano, M, Biziato, D, Brambilla, E, Donega, M, Alfaro Cervello, C, Snider, S, Salani, G, Pucci, F, Comi, Giancarlo, Garcia Verdugo, Jm, De Palma, M, Martino, Gianvito, Pluchino, S. |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty Cellular differentiation Biology Motor Activity Article 03 medical and health sciences Mice 0302 clinical medicine Neural Stem Cells Precursor cell medicine Animals Spinal cord injury Spinal Cord Injuries 030304 developmental biology 0303 health sciences Phagocytes Amniotic stem cells Cell Differentiation Recovery of Function medicine.disease Spinal cord Neural stem cell Nerve Regeneration Neuroepithelial cell medicine.anatomical_structure Treatment Outcome Spinal Cord Immunology Neurology (clinical) 030217 neurology & neurosurgery Adult stem cell |
| Popis: | Transplanted neural stem/precursor cells possess peculiar therapeutic plasticity and can simultaneously instruct several therapeutic mechanisms in addition to cell replacement. Here, we interrogated the therapeutic plasticity of neural stem/precursor cells after their focal implantation in the severely contused spinal cord. We injected syngeneic neural stem/precursor cells at the proximal and distal ends of the contused mouse spinal cord and analysed locomotor functions and relevant secondary pathological events in the mice, cell fate of transplanted neural stem/precursor cells, and gene expression and inflammatory cell infiltration at the injured site. We used two different doses of neural stem/precursor cells and two treatment schedules, either subacute (7 days) or early chronic (21 days) neural stem/precursor cell transplantation after the induction of experimental thoracic severe spinal cord injury. Only the subacute transplant of neural stem/precursor cells enhanced the recovery of locomotor functions of mice with spinal cord injury. Transplanted neural stem/precursor cells survived undifferentiated at the level of the peri-lesion environment and established contacts with endogenous phagocytes via cellular-junctional coupling. This was associated with significant modulation of the expression levels of important inflammatory cell transcripts in vivo. Transplanted neural stem/precursor cells skewed the inflammatory cell infiltrate at the injured site by reducing the proportion of 'classically-activated' (M1-like) macrophages, while promoting the healing of the injured cord. We here identify a precise window of opportunity for the treatment of complex spinal cord injuries with therapeutically plastic somatic stem cells, and suggest that neural stem/precursor cells have the ability to re-programme the local inflammatory cell microenvironment from a 'hostile' to an 'instructive' role, thus facilitating the healing or regeneration past the lesion. |
| Databáze: | OpenAIRE |
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