Effect of umbilical cord blood stem cells transplantation on bladder dysfunction induced by cerebral ischemia in rats

Taiwan J Obstet Gynecol. 2016 Oct;55(5):672-679. doi: 10.1016/j.tjog.2015.11.002.

Abstract

Objective: To demonstrate the effect of human umbilical cord blood-derived CD34+ cells on bladder dysfunction induced by cerebral ischemia in rats.

Materials and methods: Female rats were subjected to either 60 minute middle cerebral artery occlusion (MCAO) or a sham operation. Rats were divided into four groups: sham operation, MCAO without treatment, infusion with 1×106 CD34+ cells 30 minutes before MCAO, and infusion with 1×106 CD34+ cells 3 hours after MCAO. Bladder function was analyzed by cystometry at 1 day, 3 days, and 7 days after MCAO. Expressions of nerve growth factor (NGF), M2 and M3 muscarinic receptors were measured by immunohistochemistry and real time polymerase chain reaction.

Results: Cystometric results showed that, following MCAO, rats have a significant increase in peak voiding pressure and residual volume. Conversely, there is a significant decrease in voided volumes and intercontraction intervals. Cystometric variables after pre- and postischemic CD34+ treatment nearly returned to levels found in sham-operated rats. The expression of bladder NGF and M3 was decreased after MCAO, but significantly increased following preischemic CD34+ treatment. There was decreased expression of bladder M2 mRNA despite an increased level of M2 immunoreactivity at 3 days and 7 days after MCAO. Expression of bladder M2 immunoreactivity and mRNA nearly returned to sham group levels after preischemic CD34+ treatment.

Conclusion: Bladder dysfunction in a rat model caused by MCAO may be restored to normal micturition by treatment with human umbilical cord blood-derived CD34+ cells and may be related to the expressions of NGF, M2, and M3 in the bladder.

Keywords: bladder; cord blood stem cell; cystometry; middle cerebral artery occlusion; stroke.

MeSH terms

  • Animals
  • Brain Ischemia / complications
  • Brain Ischemia / surgery*
  • Cord Blood Stem Cell Transplantation / methods*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Immunohistochemistry
  • Nerve Growth Factor / biosynthesis
  • Nerve Growth Factor / genetics
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptor, Muscarinic M2 / biosynthesis
  • Receptor, Muscarinic M2 / genetics
  • Receptor, Muscarinic M3 / biosynthesis
  • Receptor, Muscarinic M3 / genetics
  • Urinary Bladder / metabolism
  • Urinary Bladder / physiopathology*
  • Urinary Bladder, Neurogenic / etiology
  • Urinary Bladder, Neurogenic / metabolism
  • Urinary Bladder, Neurogenic / physiopathology*
  • Urodynamics / physiology*

Substances

  • RNA, Messenger
  • Receptor, Muscarinic M2
  • Receptor, Muscarinic M3
  • Nerve Growth Factor