Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment

• Published in: International journal of molecular sciences 2021-05, Vol.22 (11), p.5966
• Main Authors: Bonilla, Pablo, Hernandez, Joaquim, Giraldo, Esther, González-Pérez, Miguel A, Alastrue-Agudo, Ana, Elkhenany, Hoda, Vicent, María J, Navarro, Xavier, Edel, Michael, Moreno-Manzano, Victoria
• Format: Article
• Language: English
• Subjects: Acetals - therapeutic use; Animals; Cells, Cultured; curcumin; Curcumin - pharmacology; Female; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nanoconjugates - therapeutic use; Neural Stem Cells; neuroprotection; Neuroprotective Agents - pharmacology; Polymers - therapeutic use; polymer–drug conjugate; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries - therapy; spinal cord injury; stem cells
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22115966

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-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.