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Muscle Precursor Cells for the Restoration of Irreversibly Damaged Sphincter Function: A Pre‐Clinical Study
Author(s) -
Daniel Eberli,
Shay Soker,
Yoo James,
Atala Anthony
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a644-c
Subject(s) - sphincter , urethral sphincter , myogenesis , medicine , animal model , anatomy , myocyte , muscle tissue , skeletal muscle , urology , chemistry , pathology , urethra
Background We previously have shown that mpc are able to form new myotubes within irreversibly damaged sphincters and restore functional motor units in a rat model. Current preclinical study investigated the feasibility of applying autologous cell therapy for the functional restoration of sphincters in a canine model. Methods A model of irreversible damage of the striated urinary sphincter was created by microsurgically excising approximately 50% of sphincter muscle in dogs. Autologous muscle precursor cells (mpc), isolated from skeletal muscle fibers, were grown and expanded in culture. Sphincteric function was assessed by urodynamic studies on normal as well as damaged sphincters. The culture expanded mpc were injected into the damaged muscle of the animals with sphincter insufficiency. The animals were followed up to 6 months after cell therapy, and urodynamic studies, ultrastructural, and histological examination were performed. Results Canine mpc were successfully and reproducibly isolated, grown and expanded in sufficient quantities. The animals injected with mpc showed a substantial improvement in sphincter function. The pressure that initiated leak in the cell treated animals increased 230% as compared to only 73% in the non‐injected control animals. The average sphincter pressure increased 170% in the animals with mpc injection, while the pressure in the control animals dropped by 61%. Histologically, the implanted cells that were labeled with a tracer (PKH67, Fluorescent Dye) survived to form tissue within the injected region of the sphincter. There was a minimal inflammatory response. Conclusion The injections of autologous muscle precursor cells are able to survive and form mature tissue within the damaged sphincter region.