Human-Induced Neural and Mesenchymal Stem Cell Therapy Combined with a Curcumin Nanoconjugate as a Spinal Cord Injury Treatment
Autor: | Miguel A González-Pérez, Hoda Elkhenany, Pablo Bonilla, Michael J. Edel, Ana Alastrue-Agudo, Xavier Navarro, Victoria Moreno-Manzano, María J. Vicent, Esther Giraldo, Joaquim Hernández |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Polymers
polymer-drug conjugate Nanoconjugates Pharmacology Rats Sprague-Dawley Acetals Neural Stem Cells curcumin Biology (General) Induced pluripotent stem cell Spinal cord injury Spectroscopy Cells Cultured Microglia General Medicine Neural stem cell polymer–drug conjugate Computer Science Applications Chemistry medicine.anatomical_structure Neuroprotective Agents Female neuroprotection Stem cell QH301-705.5 Induced Pluripotent Stem Cells Mesenchymal Stem Cell Transplantation Neuroprotection Catalysis Article Inorganic Chemistry stem cells medicine Animals Humans Physical and Theoretical Chemistry QD1-999 Molecular Biology Spinal Cord Injuries business.industry Organic Chemistry Mesenchymal stem cell Mesenchymal Stem Cells Recovery of Function medicine.disease spinal cord injury Rats Transplantation nervous system business |
Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 11 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) instname Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) International Journal of Molecular Sciences, Vol 22, Iss 5966, p 5966 (2021) |
ISSN: | 1422-0067 2017-2230 |
DOI: | 10.3390/ijms22115966 |
Popis: | Altres ajuts: Fundació Marató TV3 2017/refs.20172230, 20172231 i 20172110 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. |
Databáze: | OpenAIRE |
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