Engineering polysialic acid on Schwann cells using polysialyltransferase gene transfer or purified enzyme exposure for spinal cord injury transplantation.

Pearse, Damien D; Rao, Sudheendra N R; Morales, Alejo A; Wakarchuk, Warren; Rutishauser, Urs; El-Maarouf, Abderrahman; Ghosh, Mousumi

Pearse, Damien D; Rao, Sudheendra N R; Morales, Alejo A; Wakarchuk, Warren; Rutishauser, Urs; El-Maarouf, Abderrahman; Ghosh, Mousumi.

Afiliación

Pearse DD; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, 33136, USA; The Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA; The Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL,
Rao SNR; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Morales AA; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Wakarchuk W; Department of Biological Sciences, University of Alberta, Edmonton, AB, TG6 2E9, Canada.
Rutishauser U; Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, USA.
El-Maarouf A; Prothena Biosciences, South San Francisco, CA, USA.
Ghosh M; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, 33136, USA; The Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA; Department of Veterans Affairs, Veterans Affairs Medical Center, Miami, FL, 33136,

Neurosci Lett ; 748: 135690, 2021 03 23.

Article en En | MEDLINE | ID: mdl-33540059

RESUMEN

Polysialic acid (PolySia) is a critical post-translational modification on the neural cell adhesion molecule (NCAM, a.k.a., CD56), important for cell migration and axon growth during nervous system development, plasticity and repair. PolySia induction on Schwann cells (SCs) enhances their migration, axon growth support and ability to improve functional recovery after spinal cord injury (SCI) transplantation. In the current investigation two methods of PolySia induction on SCs, lentiviral vector transduction of the mouse polysialytransferase gene ST8SIA4 (LV-PST) or enzymatic engineering with a recombinant bacterial PST (PSTNm), were examined comparatively for their effects on PolySia induction, SC migration, the innate immune response and axon growth after acute SCI. PSTNm produced significant PolySia induction and a greater diversity of surface molecule polysialylation on SCs as evidenced by immunoblot. In the scratch wound assay, PSTNm was superior to LV-PST in the promotion of SC migration and gap closure. At 24 h after SCI transplantation, PolySia induction on SCs was most pronounced with LV-PST. Co-delivery of PSTNm with SCs, but not transient cell exposure, led to broader induction of PolySia within the injured spinal cord due to polysialylation upon both host cells and transplanted SCs. The innate immune response after SCI, measured by CD68 immunoreactivity, was similar among PolySia induction methods. LV-PST or PSTNm co-delivery with SCs provided a similar enhancement of SC migration and axon growth support above that of unmodified SCs. These studies demonstrate that LV-PST and PSTNm provide comparable acute effects on SC polysialation, the immune response and neurorepair after SCI.

Asunto(s)

Movimiento Celular/efectos de los fármacos; Células de Schwann/efectos de los fármacos; Ácidos Siálicos/farmacología; Sialiltransferasas/efectos de los fármacos; Traumatismos de la Médula Espinal/tratamiento farmacológico; Animales; Movimiento Celular/fisiología; Modelos Animales de Enfermedad; Ratones; Moléculas de Adhesión de Célula Nerviosa; Recuperación de la Función/efectos de los fármacos; Recuperación de la Función/fisiología; Células de Schwann/metabolismo; Sialiltransferasas/genética; Traumatismos de la Médula Espinal/fisiopatología

Palabras clave

Axon growth; Cell migration; Polysialic acid; Polysialytransferase; Schwann cell transplantation; Spinal cord injury

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células de Schwann / Ácidos Siálicos / Sialiltransferasas / Traumatismos de la Médula Espinal / Movimiento Celular Límite: Animals Idioma: En Revista: Neurosci Lett Año: 2021 Tipo del documento: Article Pais de publicación: Irlanda

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