Transplantation and repair: combined cell implantation and chondroitinase delivery prevents deterioration of bladder function in rats with complete spinal cord injury

Spinal Cord. 2009 Oct;47(10):727-32. doi: 10.1038/sc.2009.10. Epub 2009 Mar 3.

Abstract

Study design: Additional examination. In this study, we report changes in bladder function after a combined treatment that was designed to study axonal regeneration after complete spinal cord injury (SCI) in rats.

Objectives: To report effects on bladder function following the administration of a combined treatment for complete SCI.

Setting: University of Alberta, Faculty of Rehabilitation Medicine, Edmonton, Canada.

Methods: Eight rats received Schwann cells in Matrigel-filled guidance channels, olfactory ensheathing glia and chondroitinase ABC at the lesion site following complete thoracic SCI. Controls (n=7) received Matrigel only. Daily bladder examinations were performed. Analysis of bladder size, wall thickness, actin and collagen type III was performed after 14 weeks.

Results: Following SCI, both groups regained bladder voiding after 3 weeks. However, 2 weeks later, incontinence was observed in all untreated rats and two treated rats. Post-mortem examination of bladders revealed enlarged bladder sizes. Thicker bladder walls were found in untreated rats, which were composed of disorganized bundles of smooth muscle fibers surrounded by high amounts of collagen (type III).

Conclusion: We show that the combined treatment prevents collagen deposition in bladder walls and maintains the rat's ability to void efficiently. Although the mechanism responsible for this improvement is unclear, our study shows that the present combinatory therapy can influence bladder function, thus expanding their utility as a broad reparative approach for SCI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chondroitin ABC Lyase / pharmacology
  • Chondroitin ABC Lyase / therapeutic use
  • Chondroitinases and Chondroitin Lyases / pharmacology*
  • Chondroitinases and Chondroitin Lyases / therapeutic use
  • Cicatrix / drug therapy*
  • Cicatrix / physiopathology
  • Cicatrix / prevention & control
  • Collagen / metabolism
  • Collagen / pharmacology
  • Collagen / therapeutic use
  • Disease Models, Animal
  • Drug Combinations
  • Female
  • Laminin / pharmacology
  • Laminin / therapeutic use
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / pathology
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / physiology
  • Neuroglia / cytology
  • Neuroglia / physiology
  • Neuroglia / transplantation
  • Olfactory Bulb / cytology
  • Olfactory Bulb / transplantation
  • Proteoglycans / pharmacology
  • Proteoglycans / therapeutic use
  • Rats
  • Rats, Inbred F344
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Schwann Cells / cytology
  • Schwann Cells / physiology
  • Schwann Cells / transplantation
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*
  • Tissue Transplantation / methods*
  • Treatment Outcome
  • Urinary Bladder / innervation
  • Urinary Bladder / pathology
  • Urinary Bladder / physiopathology
  • Urinary Bladder, Neurogenic / etiology
  • Urinary Bladder, Neurogenic / prevention & control
  • Urinary Bladder, Neurogenic / therapy*

Substances

  • Drug Combinations
  • Laminin
  • Proteoglycans
  • matrigel
  • Collagen
  • Chondroitinases and Chondroitin Lyases
  • Chondroitin ABC Lyase