Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation After Composite Tissue Allotransplantation

Abstract

Composite Tissue Allotransplantation (CTA) offers an alternative reconstructive strategy for complicated musculoskeletal injuries incurred during modern warfare where functional outcomes after multiple conventional reconstructions are suboptimal. Broader clinical application of CTA, however, continues to be hampered by requirement for long-term multi-drug immunosuppression to prevent graft rejection. Furthermore, unlike in solid organs, clinical success is dictated not only by graft acceptance, but also by functional outcome. Our study proposes a novel cell-based therapy utilizing mesenchymal stem cells (MSC) that can augment nerve regeneration while minimizing the need for immunosuppression. After transition from University of Pittsburgh to Johns Hopkins University, we optimized our isolation and culture protocol for MSCs. Immunophenotypic and functional characterization of cultured cells demonstrated potent immunomodulatory effects of MSCs in vitro. Preliminary functional outcome analysis using Catwalk showed convergent data with similar loss and return of function among groups. Similarly, compound muscle action potentials at early time points showed small non-significant increases in amplitude in experimental groups. In contrast, normalized gastrocnemius weights showed increased muscle weight in only the systemic injection group. Overall, we continue to monitor both functional and histological outcomes. Consistent with existing literature on nerve regeneration, we expect to observe more evident differences among groups with increased data over the longer term.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2011
Accession Number
ADA559244

Entities

People

  • W. P. Lee

Organizations

  • Johns Hopkins University

Tags

DTIC Thesaurus Topics

  • Amplitude
  • Animal Structures
  • Arteries
  • Biological Staining And Labeling
  • Bone Marrow
  • Cells
  • Immunomodulation
  • Immunosuppressive Agents
  • Lymphocytes
  • Measurement
  • Osteoblasts
  • Peripheral Nervous System
  • Sciatic Nerve
  • Stem Cells
  • Stromal Cells
  • Tissues
  • Veins

Fields of Study

  • Medicine

Readers

  • Neuroscience
  • Research Science/Academic Research
  • Trauma Surgery or Emergency Medicine.

Technology Areas

  • Biotechnology