Application of the allogenic mesenchymal stem cells in the therapy of the bladder tuberculosis

J Tissue Eng Regen Med. 2018 Mar;12(3):e1580-e1593. doi: 10.1002/term.2583. Epub 2017 Dec 6.

Abstract

Urogenital tuberculosis (TB) often leads to contraction of the bladder, a reduction of the urinary reservoir capacity, and, in the latest stage, to real microcystitis up to full obliteration. Bladder TB Stage 4 is unsuitable for conservative therapy, and cystectomy with subsequent enteroplasty is indicated. In this study, using a model of bladder TB in New Zealand rabbits, the therapeutic efficacy of the interstitial injection of autologous bone-derived mesenchymal stem cells (MSCs) combined with standard anti-TB treatment in the restoration of the bladder function was demonstrated. For analysis of the MSC distribution in tissues, the latter were labelled with superparamagnetic iron oxide nanoparticles. In vitro studies demonstrated the high intracellular incorporation of nanoparticles and the absence of cytotoxicity on MSC viability and proliferation. A single-dose administration of MSCs into the bladder mucosal layer significantly reduced the wall deformation and inflammation and hindered the development of fibrosis, which was proven by the subsequent histological assay. Confocal microscopy studies of the bladder cryosections confirmed the presence of superparamagnetic iron oxide nanoparticle-labelled MSCs in different bladder layers of the treated animals, thus indicating the role of stem cells in bladder regeneration.

Keywords: Mycobacterium tuberculosis; bladder; fibrosis; mesenchymal stem cells; superparamagnetic iron oxide nanoparticles; urogenital tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Cell Differentiation
  • Cell Shape
  • Disease Models, Animal
  • Magnetite Nanoparticles / chemistry
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Rabbits
  • Transplantation, Homologous
  • Tuberculosis / drug therapy
  • Tuberculosis / pathology
  • Tuberculosis / therapy*
  • Urinary Bladder / drug effects
  • Urinary Bladder / pathology*

Substances

  • Antitubercular Agents
  • Magnetite Nanoparticles