Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment

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...

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Detalles Bibliográficos
Autores: Bonilla, Pablo, Hernández Martín, Joaquim|||0000-0003-1409-5568, Giraldo, Esther, González-Pérez, Miguel A., Alastrue-Agudo, Ana|||0000-0002-9326-2119, Elkhenany, Hoda|||0000-0003-2638-8640, Vicent, María J., Navarro, X. (Xavier)|||0000-0001-9849-902X, Edel, Michael J.|||0000-0002-5619-8680, Moreno-Manzano, Victoria|||0000-0002-6035-9491
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:250784
Acceso en línea:https://ddd.uab.cat/record/250784
https://dx.doi.org/urn:doi:10.3390/ijms22115966
Access Level:acceso abierto
Palabra clave:Spinal cord injury
Stem cells
Curcumin
Neuroprotection
Polymer-drug conjugate
Descripción
Sumario: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.

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