TY - JOUR
T1 - Muscle precursor cells for the restoration of irreversibly damaged sphincter function
AU - Eberli, Daniel
AU - Aboushwareb, Tamer
AU - Soker, Shay
AU - Yoo, James J.
AU - Atala, Anthony
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2012
Y1 - 2012
N2 - Multiple modalities, including injectable bulking agents and surgery, have been used to treat stress urinary incontinence. However, none of these methods is able to fully restore normal striated sphincter muscle function. In this study, we explored the possibility of achieving functional recovery of the urinary sphincter muscle using autologous muscle precursor cells (MPCs) as an injectable, cell-based therapy. A canine model of striated urinary sphincter insufficiency was created by microsurgically removing part of the sphincter muscle in 24 dogs. Autologous MPCs were obtained, expanded in culture, and injected into the damaged sphincter muscles of 12 animals. The animals were followed for up to 6 months after injection, and urodynamic studies, functional organ bath studies, ultrastructural and histological examinations were performed. Animals receiving MPC injections demonstrated sphincter pressures of approximately 80% of normal values, while the pressures in the control animals without cells dropped and remained at 20% of normal values. Histological analysis indicated that the implanted cells survived and formed tissue, including new innervated muscle fibers, within the injected region of the sphincter. These results indicate that autologous muscle precursor cells may be able to restore otherwise irreversibly damaged urinary sphincter function clinically.
AB - Multiple modalities, including injectable bulking agents and surgery, have been used to treat stress urinary incontinence. However, none of these methods is able to fully restore normal striated sphincter muscle function. In this study, we explored the possibility of achieving functional recovery of the urinary sphincter muscle using autologous muscle precursor cells (MPCs) as an injectable, cell-based therapy. A canine model of striated urinary sphincter insufficiency was created by microsurgically removing part of the sphincter muscle in 24 dogs. Autologous MPCs were obtained, expanded in culture, and injected into the damaged sphincter muscles of 12 animals. The animals were followed for up to 6 months after injection, and urodynamic studies, functional organ bath studies, ultrastructural and histological examinations were performed. Animals receiving MPC injections demonstrated sphincter pressures of approximately 80% of normal values, while the pressures in the control animals without cells dropped and remained at 20% of normal values. Histological analysis indicated that the implanted cells survived and formed tissue, including new innervated muscle fibers, within the injected region of the sphincter. These results indicate that autologous muscle precursor cells may be able to restore otherwise irreversibly damaged urinary sphincter function clinically.
KW - Cellular therapy
KW - Incontinence
KW - Muscle precursor cells
KW - Muscle regeneration
KW - Sphincter
UR - http://www.scopus.com/inward/record.url?scp=84869778747&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869778747&partnerID=8YFLogxK
U2 - 10.3727/096368911X623835
DO - 10.3727/096368911X623835
M3 - Article
C2 - 22236637
AN - SCOPUS:84869778747
VL - 21
SP - 2089
EP - 2098
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 9
ER -