MicroRNA-29 facilitates transplantation of bone marrow-derived mesenchymal stem cells to alleviate pelvic floor dysfunction by repressing elastin

Stem Cell Res Ther. 2016 Nov 17;7(1):167. doi: 10.1186/s13287-016-0428-7.

Abstract

Background: Pelvic floor dysfunction (PFD) is a condition affecting many women worldwide, with symptoms including stress urinary incontinence (SUI) and pelvic organ prolapse (POP). We have previously demonstrated stable elastin-expressing bone marrow-derived mesenchymal stem cells (BMSCs) attenuated PFD in rats, and aim to further study the effect of microRNA-29a-3p regulation on elastin expression and efficacy of BMSC transplantation therapy.

Methods: We inhibited endogenous microRNA-29a-3p in BMSCs and investigated its effect on elastin expression by RT-PCR and Western blot. MicroRNA-29-inhibited BMSCs were then transplanted into PFD rats, accompanied by sustained release of bFGF using formulated bFGF in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP), followed by evaluation of urodynamic tests.

Results: MicroRNA-29a-3p inhibition resulted in upregulated expression and secretion of elastin in in vitro culture of BMSCs. After co-injection with PLGA-loaded bFGF NP into the PFD rats in vivo, microRNA-29a-3p-inhibited BMSCs significantly improved the urodynamic test results.

Conclusions: Our multidisciplinary study, combining microRNA biology, genetically engineered BMSCs, and nanoparticle technology, provides an excellent stem cell-based therapy for repairing connective tissues and treating PFD.

Keywords: Bone marrow-derived mesenchymal stem cells (BMSC); Elastin; MicroRNA-29a-3p; Nanoparticles; Pelvic floor dysfunction (PFD).

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism*
  • Cells, Cultured
  • Disease Models, Animal
  • Elastin / metabolism*
  • Fibroblast Growth Factors / administration & dosage
  • Humans
  • Lactic Acid / administration & dosage
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / metabolism*
  • Nanoparticles / administration & dosage
  • Pelvic Floor / physiology
  • Pelvic Floor Disorders / metabolism*
  • Pelvic Floor Disorders / therapy*
  • Polyglycolic Acid / administration & dosage
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats

Substances

  • MIRN29a microRNA, human
  • MicroRNAs
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Fibroblast Growth Factors
  • Elastin