title: Precise injection of human mesenchymal stromal cells in the urethral sphincter complex of Göttingen minipigs without unspecific bulking effects.
abstract: OBJECTIVE
  To investigate if injection of cells in the urethral sphincter complex causes unspecific bulking effects.
  
  
  METHODS
  Human mesenchymal stromal cells were isolated, expanded, and characterized. For transurethral injection, cells were labeled with the fluorescent dye PKH26 and in magnetic resonance imaging associated experiments with superparamagnetic particles. Aliquots of cells in 250 µL solvent were injected under vision in the urethral sphincter of immuno-suppressed Göttingen minipigs. Sphincteric closure pressure was recorded by standard and high-definition urethral pressure profilometry prior to and after cell injection. The animals were sacrificed after surgery or after 3 weeks, 3, 6, or 12 months of follow-up. The localisation of the injected cells was explored by histochemistry. Sham-treated animals served as controls.
  
  
  RESULTS
  PKH26-labeled cells survive injections in sphincter tissue samples by Williams cystoscopic injection needle well. In our animal study, the cellular depots were detected in the submucosa or in deeper zones of the sphincter, depending of the length of the injection needle (4-8 mm). Adverse effects associated with injection of cells or solvent such as a noteworthy bleeding, incontinence, or obstruction, were not recorded (n = 96 minipigs). However, a transient infiltration of macrophages was detected 3 weeks after cell injection. Changes in the urethral pressure profiles were not observed in cell-treated (n = 72) compared to sham-treated animals (n = 24).
  
  
  CONCLUSIONS
  Injection of small aliquots of cells to investigate cell therapies in minipigs is a feasible and safe procedure, and it does not bias the intrinsic urethral wall pressure.
authors.affiliation: Department of Urology, University of Tübingen Hospital, Tübingen, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Amend
authors.affiliation: Department of Urology, University of Tübingen Hospital, Tübingen, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kelp
authors.affiliation: Department of Urology, University of Tübingen Hospital, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Vaegler
authors.affiliation: Institute for Systems Dynamics, University of Stuttgart, Stuttgart, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Klünder
authors.affiliation: Department of Urology, University of Tübingen Hospital, Tübingen, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Frajs
authors.affiliation: Department of Medicine II, University of Tübingen Hospital, Tübingen, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Klein
authors.affiliation: Department of Urology, University of Tübingen Hospital, Tübingen, Germany.
authors.forename: Karl-Dietrich
authors.initials: KD
authors.lastname: Sievert
authors.affiliation: Institute for Systems Dynamics, University of Stuttgart, Stuttgart, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Sawodny
authors.affiliation: Department of Urology, University of Tübingen Hospital, Tübingen, Germany.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.affiliation: Department of Urology, University of Tübingen Hospital, Tübingen, Germany.
authors.forename: Wilhelm K
authors.initials: WK
authors.lastname: Aicher
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D005260:Female; D007267:Injections; D008279:Magnetic Resonance Imaging; D059630:Mesenchymal Stem Cells; D013552:Swine; D013556:Swine, Miniature; D014521:Urethra / Q000000981:diagnostic imaging / Q000601:surgery*
keywords: cell therapy; pre-clinical animal model; urethral pressure profile; urinary incontinence