The dose-effect safety profile of skeletal muscle precursor cell therapy in a dog model of intrinsic urinary sphincter deficiency

J. Koudy Williams, Delrae Eckman, Ashley Dean, Mahmoudreza Moradi, Julie Allickson, J. Mark Cline, James J. Yoo, Anthony Atala

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Locally injected skeletal muscle precursor cells (skMPCs) integrate into and restore the muscle layers, innervation, vasculature, and function of the sphincter complex in animal models of intrinsic urinary sphincter deficiency (ISD). The goal of the present study was to test the dose-effect safety profile of skMPC therapy in a dog model of ISD. Sphincter deficiency was created in 20 adult female dogs by surgically removing the skeletal muscle layer of the urinary sphincter complex. skMPCs isolated from the hind leg were expanded in culture and injected 4 weeks later into the sphincter complex at a dose of 25 million cells (n = 5), 50 million cells (n = 5), or 100 million cells (n = 5) per milliliter in a 2-ml volume. Five dogs received no sphincter injection. The measures of maximal sphincter pressure, complete blood count, and blood chemistry were performed monthly until their sacrifice at 9 months. At that point, full necropsy was performed to assess the safety of the skMPC injections. Injection of different doses of cells had no effects on the body weight, blood cell count, or kidney or liver function test results (p>.05 among the skMPC doses). Some incidental pathologic features were found in the lower urinary tract in all groups and were most likely associated with repeat catheterization. The maximal urinary sphincter pressure was higher in the 50 million cells per milliliter treatment group than in the other experimental groups (p < .05). The findings of the present study have confirmed that urinary sphincter injection of skMPCs results in no significant local or systemic pathologic features within the dose range thatimproves sphincter pressures.

Original languageEnglish
Pages (from-to)286-294
Number of pages9
JournalStem cells translational medicine
Volume4
Issue number3
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Maximal urethral pressure
  • Pathology
  • Skeletal muscle
  • Stem cells
  • Urinary incontinence

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

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    Koudy Williams, J., Eckman, D., Dean, A., Moradi, M., Allickson, J., Mark Cline, J., Yoo, J. J., & Atala, A. (2015). The dose-effect safety profile of skeletal muscle precursor cell therapy in a dog model of intrinsic urinary sphincter deficiency. Stem cells translational medicine, 4(3), 286-294. https://doi.org/10.5966/sctm.2014-0114