Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts

René Yiou, James J. Yoo, Anthony Atala

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Background. Urinary incontinence is a debilitating condition that affects primarily elderly individuals. One major mechanism results from chronic denervation of the striated urethral sphincter with associated fibrosis. The authors investigated the fate of muscle precursor cells (MPC) injected into a model of striated urethral sphincter injury that reproduces the histopathologic changes of sphincter insufficiency. Methods. The striated urethral sphincter of older male rats was damaged by electrocoagulation. MPC were isolated from limb myofiber explants, infected with an adenovirus carrying the transgene encoding β-galactosidase, and injected into the sphincter of the same animal 37 days after injury. Animals were killed 5 and 30 days after injection for assessment of sphincter function and the formation of motor units. Results. Electrocoagulation resulted in an irreversible destruction of both sphincteric myofibers and nerve endings, with a functional incapacity of the damaged sphincter to sustain an increase in bladder pressure; atrophy and fibrosis developed after 1 month. Injection of MPC resulted in the formation of β-galactosidase- expressing myotubes in the sphincter that persisted beyond 30 days. The regenerated myotubes carried acetylcholine receptors associated with a nerve ending and were thus considered to form anatomic motor units. Urodynamic studies confirmed the restoration of 41% of sphincter function 1 month after MPC injection. Conclusions. The authors showed that MPC isolated from limb muscles of an older animal can recapitulate a myogenic program when injected into an irreversibly injured sphincter. The maturation of MPC activates nerve regeneration and restores functional motor units.

Original languageEnglish
Pages (from-to)1053-1060
Number of pages8
JournalTransplantation
Volume76
Issue number7
DOIs
StatePublished - Oct 15 2003
Externally publishedYes

Fingerprint

Myoblasts
Autografts
Wounds and Injuries
Urethra
Galactosidases
Electrocoagulation
Nerve Endings
Skeletal Muscle Fibers
Injections
Fibrosis
Extremities
Nerve Regeneration
Urodynamics
Urinary Incontinence
Cholinergic Receptors
Denervation
Transgenes
Adenoviridae
Atrophy
Urinary Bladder

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts. / Yiou, René; Yoo, James J.; Atala, Anthony.

In: Transplantation, Vol. 76, No. 7, 15.10.2003, p. 1053-1060.

Research output: Contribution to journalArticle

Yiou, René ; Yoo, James J. ; Atala, Anthony. / Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts. In: Transplantation. 2003 ; Vol. 76, No. 7. pp. 1053-1060.
@article{29cdce2462c547f9b0bd54190fdf5dd3,
title = "Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts",
abstract = "Background. Urinary incontinence is a debilitating condition that affects primarily elderly individuals. One major mechanism results from chronic denervation of the striated urethral sphincter with associated fibrosis. The authors investigated the fate of muscle precursor cells (MPC) injected into a model of striated urethral sphincter injury that reproduces the histopathologic changes of sphincter insufficiency. Methods. The striated urethral sphincter of older male rats was damaged by electrocoagulation. MPC were isolated from limb myofiber explants, infected with an adenovirus carrying the transgene encoding β-galactosidase, and injected into the sphincter of the same animal 37 days after injury. Animals were killed 5 and 30 days after injection for assessment of sphincter function and the formation of motor units. Results. Electrocoagulation resulted in an irreversible destruction of both sphincteric myofibers and nerve endings, with a functional incapacity of the damaged sphincter to sustain an increase in bladder pressure; atrophy and fibrosis developed after 1 month. Injection of MPC resulted in the formation of β-galactosidase- expressing myotubes in the sphincter that persisted beyond 30 days. The regenerated myotubes carried acetylcholine receptors associated with a nerve ending and were thus considered to form anatomic motor units. Urodynamic studies confirmed the restoration of 41{\%} of sphincter function 1 month after MPC injection. Conclusions. The authors showed that MPC isolated from limb muscles of an older animal can recapitulate a myogenic program when injected into an irreversibly injured sphincter. The maturation of MPC activates nerve regeneration and restores functional motor units.",
author = "Ren{\'e} Yiou and Yoo, {James J.} and Anthony Atala",
year = "2003",
month = "10",
day = "15",
doi = "10.1097/01.TP.0000090396.71097.C2",
language = "English",
volume = "76",
pages = "1053--1060",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts

AU - Yiou, René

AU - Yoo, James J.

AU - Atala, Anthony

PY - 2003/10/15

Y1 - 2003/10/15

N2 - Background. Urinary incontinence is a debilitating condition that affects primarily elderly individuals. One major mechanism results from chronic denervation of the striated urethral sphincter with associated fibrosis. The authors investigated the fate of muscle precursor cells (MPC) injected into a model of striated urethral sphincter injury that reproduces the histopathologic changes of sphincter insufficiency. Methods. The striated urethral sphincter of older male rats was damaged by electrocoagulation. MPC were isolated from limb myofiber explants, infected with an adenovirus carrying the transgene encoding β-galactosidase, and injected into the sphincter of the same animal 37 days after injury. Animals were killed 5 and 30 days after injection for assessment of sphincter function and the formation of motor units. Results. Electrocoagulation resulted in an irreversible destruction of both sphincteric myofibers and nerve endings, with a functional incapacity of the damaged sphincter to sustain an increase in bladder pressure; atrophy and fibrosis developed after 1 month. Injection of MPC resulted in the formation of β-galactosidase- expressing myotubes in the sphincter that persisted beyond 30 days. The regenerated myotubes carried acetylcholine receptors associated with a nerve ending and were thus considered to form anatomic motor units. Urodynamic studies confirmed the restoration of 41% of sphincter function 1 month after MPC injection. Conclusions. The authors showed that MPC isolated from limb muscles of an older animal can recapitulate a myogenic program when injected into an irreversibly injured sphincter. The maturation of MPC activates nerve regeneration and restores functional motor units.

AB - Background. Urinary incontinence is a debilitating condition that affects primarily elderly individuals. One major mechanism results from chronic denervation of the striated urethral sphincter with associated fibrosis. The authors investigated the fate of muscle precursor cells (MPC) injected into a model of striated urethral sphincter injury that reproduces the histopathologic changes of sphincter insufficiency. Methods. The striated urethral sphincter of older male rats was damaged by electrocoagulation. MPC were isolated from limb myofiber explants, infected with an adenovirus carrying the transgene encoding β-galactosidase, and injected into the sphincter of the same animal 37 days after injury. Animals were killed 5 and 30 days after injection for assessment of sphincter function and the formation of motor units. Results. Electrocoagulation resulted in an irreversible destruction of both sphincteric myofibers and nerve endings, with a functional incapacity of the damaged sphincter to sustain an increase in bladder pressure; atrophy and fibrosis developed after 1 month. Injection of MPC resulted in the formation of β-galactosidase- expressing myotubes in the sphincter that persisted beyond 30 days. The regenerated myotubes carried acetylcholine receptors associated with a nerve ending and were thus considered to form anatomic motor units. Urodynamic studies confirmed the restoration of 41% of sphincter function 1 month after MPC injection. Conclusions. The authors showed that MPC isolated from limb muscles of an older animal can recapitulate a myogenic program when injected into an irreversibly injured sphincter. The maturation of MPC activates nerve regeneration and restores functional motor units.

UR - http://www.scopus.com/inward/record.url?scp=0142103678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142103678&partnerID=8YFLogxK

U2 - 10.1097/01.TP.0000090396.71097.C2

DO - 10.1097/01.TP.0000090396.71097.C2

M3 - Article

VL - 76

SP - 1053

EP - 1060

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 7

ER -