Bone-marrow mononuclear cell therapy in a mouse model of amyotrophic lateral sclerosis: Functional outcomes from different administration routes

Brain Res. 2019 Jun 1:1712:73-81. doi: 10.1016/j.brainres.2019.02.003. Epub 2019 Feb 5.

Abstract

Amyotrophic lateral sclerosis (ALS) is a chronic degenerative disease that mainly affects motor neurons, leading to progressive paralysis and death. Recently, cell therapy has emerged as a therapeutic alternative for several neurological diseases, including ALS, and bone-marrow cells are one of the major cell sources. Considering the importance of pre-clinical trials to determine the best therapeutic protocol and the hope of translating this protocol to the clinical setting, we tested bone-marrow mononuclear cell (BMMC) therapy administered by different routes in the SOD1G93A model of ALS. BMMCs were isolated from non-transgenic, age matched animals and administered intravenously (IV), intramuscularly (IM), and intravenously and intramuscular concomitantly (IV + IM). BMMC therapy had no significant beneficial effects when injected IV or IM, but delayed disease progression when these two routes were used concomitantly. BMMC IV + IM treatment reduced the number of microglia cells in the spinal cord and partially protected of neuromuscular-junction innervation, but had no effect in preventing motor-neuron loss. This study showed that injection of BMMC IV + IM had better results when compared to each route in isolation, highlighting the importance of targeting multiple anatomical regions in the treatment of ALS.

Keywords: Amyotrophic lateral sclerosis; Bone-marrow mononuclear cells; Cell therapy; Microglia cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous / methods
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Bone Marrow / metabolism
  • Cell- and Tissue-Based Therapy / methods*
  • Disease Models, Animal
  • Disease Progression
  • Injections, Intramuscular / methods
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism
  • Neuromuscular Junction / metabolism
  • Spinal Cord / metabolism
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1 / metabolism

Substances

  • Superoxide Dismutase
  • Superoxide Dismutase-1