Human-induced neural and mesenchymal stem cell therapy combined with a curcumin nanoconjugate as a spinal cord injury treatment
Bonilla, Pablo (Centro de Investigación Príncipe Felipe (València))
Hernández Martín, Joaquim (Universitat Autònoma de Barcelona. Institut de Neurociències)
Giraldo, Esther (Universitat Politècnica de València. Departament de Biotecnologia)
González-Pérez, Miguel A. (Centro de Investigación Príncipe Felipe (València))
Alastrue-Agudo, Ana (Centro de Investigación Príncipe Felipe (València))
Elkhenany, Hoda (Centro de Investigación Príncipe Felipe (València))
Vicent, María J. (Centro de Investigación Príncipe Felipe. Laboratorio de Terapéutica de Polímeros)
Navarro, X. (Xavier) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Edel, Michael J. (Institut Barraquer)
Moreno-Manzano, Victoria (Centro de Investigación Príncipe Felipe (València))

Date:	2021
Abstract:	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.
Grants:	Agencia Estatal de Investigación RTI2018-095872-B-C21
Note:	Altres ajuts: Fundació Marató TV3 2017/refs.20172230, 20172231 i 20172110
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Spinal cord injury ; Stem cells ; Curcumin ; Neuroprotection ; Polymer-drug conjugate
Published in:	International journal of molecular sciences, Vol. 22, Issue 11 (June 2021) , art. 5966, ISSN 1422-0067

DOI: 10.3390/ijms22115966
PMID: 34073117

25 p, 5.7 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles