Endoscopic injection of skeletal muscle-derived cells augments gut smooth muscle sphincter function: implications for a novel therapeutic approach

Pankaj Jay Pasricha, Ijaz Ahmed, Ron J. Jankowski, Maria Adelaide Micci

Research output: Contribution to journalArticle

Abstract

Introduction: Sphincter function is a common problem in gastroenterology and leads to disorders such as GERD and fecal incontinence. Objective: We hypothesized that transplantation of skeletal muscle-derived cells (MDCs) into GI sphincters may improve their function, leading to a more physiological approach to treating these disorders. Design: We performed experiments to test the potential of MDCs to survive and differentiate within the GI smooth muscle in order to gain further knowledge on the biology of skeletal muscle transplantation in GI smooth muscle sphincters as well as to test the safety and feasibility of endoscopic injection of MDCs in a large animal model. Setting: Animal laboratory. Interventions: Adult male Sprague-Dawley rats and adult male beagle dogs were used. Rat-derived and dog-derived MDCs were prepared in vitro and labeled with DiI. DiI-labeled, rat-derived MDCs (200,000/4 μL phosphate buffered saline solution) were injected bilaterally in the pyloric wall of rats, and survival, differentiation, and in vitro contractility were assessed 1 month after transplantation. Dog-derived MDCs (4.0 × 106 cells) were also injected into the lower esophageal sphincter of 3 beagle dogs by using a standard variceal sclerotherapy needle after baseline esophageal manometry and pH monitoring. The dogs were treated with daily cyclosporine, and 2 weeks later esophageal manometry was repeated and the esophagus was examined histologically. Differentiation of grafted cells was assessed by immunofluorescence, using specific antibodies to markers of the smooth muscle phenotype (smooth muscle actin) and of the skeletal muscle phenotype (skeletal muscle myosin). Results: In rats, grafted MDCs were visualized based on DiI fluorescence and were found to be localized within the muscle wall and in the muscularis mucosa. In vitro organ bath studies showed a significant increase in the contractile response of the pyloric sphincter to exogenous acetylcholine. In dogs, MDC injection resulted in a significant increase in baseline lower esophageal sphincter pressure. Further, in 1 dog with significant baseline acid reflux, MDC injection resulted in a reduction of acid reflux, with the fraction of time with pH

Original languageEnglish (US)
Pages (from-to)1231-1237
Number of pages7
JournalGastrointestinal Endoscopy
Volume70
Issue number6
DOIs
StatePublished - Dec 2009
Externally publishedYes

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Muscle Cells
Smooth Muscle
Skeletal Muscle
Injections
Dogs
Lower Esophageal Sphincter
Therapeutics
Transplantation
Manometry
Skeletal Muscle Myosins
Esophageal pH Monitoring
Phenotype
Fecal Incontinence
Acids
Sclerotherapy
Pylorus
Laboratory Animals
Gastroenterology
Gastroesophageal Reflux
Baths

ASJC Scopus subject areas

  • Gastroenterology
  • Radiology Nuclear Medicine and imaging

Cite this

Endoscopic injection of skeletal muscle-derived cells augments gut smooth muscle sphincter function : implications for a novel therapeutic approach. / Pasricha, Pankaj Jay; Ahmed, Ijaz; Jankowski, Ron J.; Micci, Maria Adelaide.

In: Gastrointestinal Endoscopy, Vol. 70, No. 6, 12.2009, p. 1231-1237.

Research output: Contribution to journalArticle

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