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15| Volume 211, P206, April 2017

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Optimal delivery route of mesoangioblasts for stem cell therapy in rat model for simulated vaginal birth injury

      Introduction and aim of the study: Stem cell therapy could be used in the treatment for pelvic floor dysfunction, either for treatment or in prevention. For both there is an experimental basis [
      • Carr L.K.
      • Robert M.
      • Kultgen P.L.
      • Herschorn S.
      • Birch C.
      • Murphy M.
      • et al.
      Autologous muscle derived cell therapy for stress urinary incontinence: a prospective, dose ranging study.
      ,
      • Lin C.S.
      • Lue T.F.
      Stem cell therapy for stress urinary incontinence: a critical review.
      ], yet the mechanism of action, optimal administration route, dose and cell type need to be determined. We aimed to investigate the fate of mesoangioblasts (MABs) when administered via local, intravenous (IV) or intra-arterial (IA) injections, using vaginal birth injury model.
      Materials and methods: 30 virgin Sprague-Dawley female rats underwent simulated vaginal birth injury [
      • Damaser M.S.
      • Broxton-King C.
      • Ferguson C.
      • Kim F.J.
      • Kerns J.M.
      Functional and neuroanatomical effects of vaginal distention and pudendal nerve crush in the female rat.
      ]. One hour after the injury, rats (n = 10) were randomly assigned to receive 2 × 106 MABs-eGFP-fLuc either local (perivaginal), IV (tail vein) or IA (bilateral at common iliac arteries). Viable MABs were tracked in vivo in the pelvic area by bioluminescence imaging (BLI) at 0d, 1d and 3 d, and ex vivo in pelvic floor organs and lungs at 3d. Further, in situ tracking of MABs was determined at 3d and 7d by RT-PCR.
      Results: Following IV injection, most of the MABs were found in the lungs and tail at all time points. Local injection was associated with the highest amount of MABs at 0d. However in the IA group, the amount of MABs increased significantly at 1d. All groups showed a significant decrease of MABs at 3d, yet with the highest remaining cell number in the IA group.
      Interpretation of results: IV injection is the least invasive route, yet the majority of cells can be found in the lungs. IA injection is an interesting route since MABs were found more locally and persisting longer, increasing the likelihood of engraftment. Following local injection there was a quick drop in MABs, yet for unknown reasons.
      Conclusions: Intra-arterial injections of MABs resulted in a more efficient homing and distribution of mesoangioblasts in the target organs.

      References

        • Carr L.K.
        • Robert M.
        • Kultgen P.L.
        • Herschorn S.
        • Birch C.
        • Murphy M.
        • et al.
        Autologous muscle derived cell therapy for stress urinary incontinence: a prospective, dose ranging study.
        J Urol. 2013; 189: 595-601
        • Lin C.S.
        • Lue T.F.
        Stem cell therapy for stress urinary incontinence: a critical review.
        Stem Cells Develop. 2012; 21: 834-843
        • Damaser M.S.
        • Broxton-King C.
        • Ferguson C.
        • Kim F.J.
        • Kerns J.M.
        Functional and neuroanatomical effects of vaginal distention and pudendal nerve crush in the female rat.
        J Urol. 2003 Sep; 170: 1027-1031