Your browser doesn't support javascript.
loading
Engineered extracellular vesicle-based gene therapy for the treatment of discogenic back pain.
Tang, Shirley N; Salazar-Puerta, Ana I; Heimann, Mary K; Kuchynsky, Kyle; Rincon-Benavides, María A; Kordowski, Mia; Gunsch, Gilian; Bodine, Lucy; Diop, Khady; Gantt, Connor; Khan, Safdar; Bratasz, Anna; Kokiko-Cochran, Olga; Fitzgerald, Julie; Laudier, Damien M; Hoyland, Judith A; Walter, Benjamin A; Higuita-Castro, Natalia; Purmessur, Devina.
Affiliation
  • Tang SN; Department of Biomedical Engineering, College of Engineering, The Ohio State University, USA.
  • Salazar-Puerta AI; Department of Biomedical Engineering, College of Engineering, The Ohio State University, USA.
  • Heimann MK; Department of Biomedical Engineering, College of Engineering, The Ohio State University, USA.
  • Kuchynsky K; Department of Biomedical Engineering, College of Engineering, The Ohio State University, USA.
  • Rincon-Benavides MA; Biophysics Graduate Program, The Ohio State University, USA.
  • Kordowski M; Biophysics Graduate Program, The Ohio State University, USA.
  • Gunsch G; Department of Biomedical Engineering, College of Engineering, The Ohio State University, USA.
  • Bodine L; Department of Mechanical Engineering, College of Engineering, The Ohio State University, USA.
  • Diop K; Department of Biology, College of Arts and Sciences, The Ohio State University, USA.
  • Gantt C; Department of Biomedical Engineering, College of Engineering, The Ohio State University, USA.
  • Khan S; Department of Orthopedics, The Ohio State University Wexner Medical Center, USA.
  • Bratasz A; Small Animal Imaging Center Shared Resources, Wexner Medical Center, USA.
  • Kokiko-Cochran O; Department of Neuroscience, The Ohio State University, USA; Institute for Behavioral Medicine Research, Neurological Institute, The Ohio State University, USA.
  • Fitzgerald J; Department of Neuroscience, The Ohio State University, USA; Institute for Behavioral Medicine Research, Neurological Institute, The Ohio State University, USA.
  • Laudier DM; Leni and Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, USA.
  • Hoyland JA; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, The University of Manchester, Manchester, UK; NIHR Manchester Musculoskeletal Biomedical Research Centre, Manchester University, NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
  • Walter BA; Department of Biomedical Engineering, College of Engineering, The Ohio State University, USA; Department of Orthopedics, The Ohio State University Wexner Medical Center, USA.
  • Higuita-Castro N; Department of Biomedical Engineering, College of Engineering, The Ohio State University, USA; Biophysics Graduate Program, The Ohio State University, USA; Department of Neurosurgery, The Ohio State University, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, USA. E
  • Purmessur D; Department of Biomedical Engineering, College of Engineering, The Ohio State University, USA; Department of Orthopedics, The Ohio State University Wexner Medical Center, USA. Electronic address: Purmessurwalter.1@osu.edu.
Biomaterials ; 308: 122562, 2024 Jul.
Article in En | MEDLINE | ID: mdl-38583365
ABSTRACT
Painful musculoskeletal disorders such as intervertebral disc (IVD) degeneration associated with chronic low back pain (termed "Discogenic back pain", DBP), are a significant socio-economic burden worldwide and contribute to the growing opioid crisis. Yet there are very few if any successful interventions that can restore the tissue's structure and function while also addressing the symptomatic pain. Here we have developed a novel non-viral gene therapy, using engineered extracellular vesicles (eEVs) to deliver the developmental transcription factor FOXF1 to the degenerated IVD in an in vivo model. Injured IVDs treated with eEVs loaded with FOXF1 demonstrated robust sex-specific reductions in pain behaviors compared to control groups. Furthermore, significant restoration of IVD structure and function in animals treated with FOXF1 eEVs were observed, with significant increases in disc height, tissue hydration, proteoglycan content, and mechanical properties. This is the first study to successfully restore tissue function while modulating pain behaviors in an animal model of DBP using eEV-based non-viral delivery of transcription factor genes. Such a strategy can be readily translated to other painful musculoskeletal disorders.
Subject(s)
Key words
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Database: MEDLINE Main subject: Genetic Therapy / Intervertebral Disc Degeneration / Extracellular Vesicles Limits: Animals Language: En Journal: Biomaterials Year: 2024 Type: Article Affiliation country: United States
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Database: MEDLINE Main subject: Genetic Therapy / Intervertebral Disc Degeneration / Extracellular Vesicles Limits: Animals Language: En Journal: Biomaterials Year: 2024 Type: Article Affiliation country: United States