Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra

Urology. 2003 Nov;62(5):958-63. doi: 10.1016/s0090-4295(03)00679-4.


Objectives: To study the physiologic outcome of allogenic transplant of muscle-derived progenitor cells (MDPCs) in the denervated female rat urethra.

Methods: MDPCs were isolated from muscle biopsies of normal 6-week-old Sprague-Dawley rats and purified using the preplate technique. Sciatic nerve-transected rats were used as a model of stress urinary incontinence. The experimental group was divided into three subgroups: control, denervated plus 20 microL saline injection, and denervated plus allogenic MDPCs (1 to 1.5 x 10(6) cells) injection. Two weeks after injection, urethral muscle strips were prepared and underwent electrical field stimulation. The pharmacologic effects of d-tubocurare, phentolamine, and tetrodotoxin on the urethral strips were assessed by contractions induced by electrical field stimulation. The urethral tissues also underwent immunohistochemical staining for fast myosin heavy chain and CD4-activated lymphocytes.

Results: Urethral denervation resulted in a significant decrease of the maximal fast-twitch muscle contraction amplitude to only 8.77% of the normal urethra and partial impairment of smooth muscle contractility. Injection of MDPCs into the denervated sphincter significantly improved the fast-twitch muscle contraction amplitude to 87.02% of normal animals. Immunohistochemistry revealed a large amount of new skeletal muscle fiber formation at the injection site of the urethra with minimal inflammation. CD4 staining showed minimal lymphocyte infiltration around the MDPC injection sites.

Conclusions: Urethral denervation resulted in near-total abolishment of the skeletal muscle and partial impairment of smooth muscle contractility. Allogenic MDPCs survived 2 weeks in sciatic nerve-transected urethra with minimal inflammation. This is the first report of the restoration of deficient urethral sphincter function through muscle-derived progenitor cell tissue engineering. MDPC-mediated cellular urethral myoplasty warrants additional investigation as a new method to treat stress urinary incontinence.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Denervation
  • Electric Stimulation
  • Female
  • Lymphocyte Activation
  • Mesenchymal Stem Cells*
  • Models, Animal
  • Muscle Contraction* / drug effects
  • Muscle, Skeletal / cytology
  • Muscle, Smooth / physiopathology
  • Muscle, Smooth / surgery*
  • Myosin Heavy Chains / analysis
  • Phentolamine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / injuries
  • Stem Cell Transplantation*
  • Tetrodotoxin / pharmacology
  • Transplantation, Homologous
  • Tubocurarine / pharmacology
  • Urethra / drug effects
  • Urethra / innervation
  • Urethra / surgery*
  • Urinary Incontinence, Stress / surgery


  • Tetrodotoxin
  • Myosin Heavy Chains
  • Tubocurarine
  • Phentolamine