Recombinant GABAergic Cells as a Therapy for Chronic Neuropathic Pain

Abstract

The main focus of the project is a development of recombinant cell-based therapy for chronic pain. Scope: The reduction in the GABA signaling and its relation to the development of chronic pain has been described after spinal cord and peripheral nerve injuries. Transplantation of GABAergic neuronal cells may restore the inhibitory potential in the spinal cord and replace dysfunctional interneurons. Grafted cells may also release additional analgesic peptides by means of genetic engineering to further enhance the benefits of this approach. Conopeptides are ideal candidates for recombinant expression using cell based strategies. The goal of the project is to develop transplantable recombinant GABAergic cells releasing MVIIA that can alleviate pain-like behavior in models of neuropathic pain after peripheral and spinal cord injury. Major findings: We have engineered and characterized the GABAergic progenitors expressing MVIIA. Recombinant and nonrecombinant cells were intra spinally injected into animals in the models of peripheral nerve injury and spinal cord injury. We have observed beneficial effects of the grafted cells in reducing hypersensitivity in all grafted animals, especially in the recombinant group. Injection of MVIIA antibody reduces the analgesic effect of the recombinant graft. The level of pain-related cytokines was reduced in the grafted animals and correlation between these pain markers and actual behavior was detected.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2021
Accession Number
AD1138283

Entities

People

  • Stanislava Jergová

Organizations

  • University of Miami

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Animals
  • Antibodies
  • Biomedical Research
  • Blood-Brain Barrier
  • Cell Physiological Processes
  • Cells
  • Cytokines
  • Engineering
  • Genetic Engineering
  • Hypersensitivity
  • Medical Personnel
  • Nerves
  • Neurons
  • Pain
  • Peripheral Nervous System
  • Proteins
  • Spinal Cord
  • Spinal Injuries
  • Students
  • Surgery
  • Test And Evaluation
  • Tissues
  • Transplantation

Fields of Study

  • Biology
  • Medicine

Readers

  • Neuroscience
  • Neurotrauma and Rehabilitation Medicine.
  • Trauma Surgery or Emergency Medicine.

Technology Areas

  • Biotechnology