Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment
Por:
P. BONILLA, J. HERNANDEZ, E. GIRALDO, M. GONZALEZ-PEREZ, A. ALASTRUE-AGUDO, H. ELKHENANY, M. VICENT, X. NAVARRO, M. EDEL and V. MORENO-MANZANO
Publicada:
1 jun 2021
Resumen:
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 mesenchymal stem cells (MSC), and a pH-responsive polyacetal-curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-kappa B (NF-kappa B) 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 beta-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.
Filiaciones:
:
Ctr Invest Principe Felipe, Neuronal & Tissue Regenerat Lab, Valencia 46012, Spain
J. HERNANDEZ:
Univ Autonoma Barcelona, Inst Neurosci, Dept Cell Biol Physiol & Immunol, Neuroplast & Regenerat Grp, Bellaterra 08193, Spain
CIBERNED, Bellaterra 08193, Spain
:
Ctr Invest Principe Felipe, Neuronal & Tissue Regenerat Lab, Valencia 46012, Spain
Univ Politecn Valencia, Dept Biotechnol, Valencia 46022, Spain
:
Ctr Invest Principe Felipe, Neuronal & Tissue Regenerat Lab, Valencia 46012, Spain
:
Ctr Invest Principe Felipe, Neuronal & Tissue Regenerat Lab, Valencia 46012, Spain
:
Ctr Invest Principe Felipe, Neuronal & Tissue Regenerat Lab, Valencia 46012, Spain
Alexandria Univ, Fac Vet Med, Dept Surg, Alexandria 22785, Egypt
:
Ctr Invest Principe Felipe, Polymer Therapeut Lab, Valencia 46012, Spain
X. NAVARRO:
Univ Autonoma Barcelona, Inst Neurosci, Dept Cell Biol Physiol & Immunol, Neuroplast & Regenerat Grp, Bellaterra 08193, Spain
CIBERNED, Bellaterra 08193, Spain
M. EDEL:
Inst Barraquer, Lab Regenerat Med, Barcelona 08021, Spain
:
Ctr Invest Principe Felipe, Neuronal & Tissue Regenerat Lab, Valencia 46012, Spain
Gold, Green Published
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