Título:
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Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment
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Autor/a:
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Bonilla, Pablo; Hernández Martín, Joaquim; Giraldo, Esther; González-Pérez, Miguel A.; Alastrue-Agudo, Ana; Elkhenany, Hoda; Vicent, María J.; Navarro, X. (Xavier); Edel, Michael J..; Moreno-Manzano, Victoria
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Abstract:
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Altres ajuts: Fundació Marató TV3 2017/refs.20172230, 20172231 i 20172110 |
Abstract:
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We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesen-chymal stem cells (MSC), and a pH-responsive polyacetal-curcumin nanoconjugate (PA-C) that al-lows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment pro-tected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccha-ride-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments. |
Materia(s):
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-Spinal cord injury -Stem cells -Curcumin -Neuroprotection -Polymer-drug conjugate |
Derechos:
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open access
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https://creativecommons.org/licenses/by/4.0/ |
Tipo de documento:
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Article |
Editor:
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Uri:
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https://ddd.uab.cat/record/250784
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