Adipose-derived stem cell conditioned medium impacts asymptomatic peripheral neuromuscular denervation in the mutant superoxide dismutase (G93A) transgenic mouse model of amyotrophic lateral sclerosis

Chandler Walker, Rena M. Meadows, Stephanie Merfeld-Clauss, Yansheng Du, Keith L. March, Kathryn Jones

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ?47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treatment could ameliorate neuromuscular junction (NMJ) disruption. Objective: To determine whether pre-symptom administration of ASC-CM prevents early NMJ disconnection. Methods:We confirmed the NMJ denervation time course in mSOD1G93A mice using co-labeling of neurofilament and postsynaptic acetylcholine receptors (AchR) by -bungarotoxin. We determined whether ASC-CM ameliorates early NMJ loss in mSOD1G93A mice by systemically administering 200l ASC-CM or vehicle medium daily from post-natal days 35 to 47 and quantifying intact NMJs through co-labeling of neurofilament and synaptophysin with -bungarotoxin in gastrocnemius muscle. Results: Intact NMJs were significantly decreased in 47 day old mSOD1G93A mice (p < 0.05), and daily systemic ASC-CM prevented disease-induced NMJ denervation compared to vehicle treated mice (p < 0.05). Conclusions: Our results lay the foundation for testing the long-term neurological benefits of systemic ASC-CM therapy in the mSOD1G93A mouse model of ALS.

Original languageEnglish (US)
Pages (from-to)621-627
Number of pages7
JournalRestorative Neurology and Neuroscience
Volume36
Issue number5
DOIs
StatePublished - Jan 1 2018

Fingerprint

Amyotrophic Lateral Sclerosis
Denervation
Conditioned Culture Medium
Transgenic Mice
Superoxide Dismutase
Stem Cells
Neuromuscular Junction
Bungarotoxins
Intermediate Filaments
Neuromuscular Junction Diseases
Synaptophysin
Motor Neurons
Cholinergic Receptors
Paralysis
Axons
Skeletal Muscle
Therapeutics

Keywords

  • adipose-derived stem cells
  • ALS
  • Amyotrophic lateral sclerosis
  • conditioned medium
  • neuromuscular junctions

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

@article{a598da96de3141d1938a767956d38b27,
title = "Adipose-derived stem cell conditioned medium impacts asymptomatic peripheral neuromuscular denervation in the mutant superoxide dismutase (G93A) transgenic mouse model of amyotrophic lateral sclerosis",
abstract = "Background: Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ?47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treatment could ameliorate neuromuscular junction (NMJ) disruption. Objective: To determine whether pre-symptom administration of ASC-CM prevents early NMJ disconnection. Methods:We confirmed the NMJ denervation time course in mSOD1G93A mice using co-labeling of neurofilament and postsynaptic acetylcholine receptors (AchR) by -bungarotoxin. We determined whether ASC-CM ameliorates early NMJ loss in mSOD1G93A mice by systemically administering 200l ASC-CM or vehicle medium daily from post-natal days 35 to 47 and quantifying intact NMJs through co-labeling of neurofilament and synaptophysin with -bungarotoxin in gastrocnemius muscle. Results: Intact NMJs were significantly decreased in 47 day old mSOD1G93A mice (p < 0.05), and daily systemic ASC-CM prevented disease-induced NMJ denervation compared to vehicle treated mice (p < 0.05). Conclusions: Our results lay the foundation for testing the long-term neurological benefits of systemic ASC-CM therapy in the mSOD1G93A mouse model of ALS.",
keywords = "adipose-derived stem cells, ALS, Amyotrophic lateral sclerosis, conditioned medium, neuromuscular junctions",
author = "Chandler Walker and Meadows, {Rena M.} and Stephanie Merfeld-Clauss and Yansheng Du and March, {Keith L.} and Kathryn Jones",
year = "2018",
month = "1",
day = "1",
doi = "10.3233/RNN-180820",
language = "English (US)",
volume = "36",
pages = "621--627",
journal = "Restorative Neurology and Neuroscience",
issn = "0922-6028",
publisher = "IOS Press",
number = "5",

}

TY - JOUR

T1 - Adipose-derived stem cell conditioned medium impacts asymptomatic peripheral neuromuscular denervation in the mutant superoxide dismutase (G93A) transgenic mouse model of amyotrophic lateral sclerosis

AU - Walker, Chandler

AU - Meadows, Rena M.

AU - Merfeld-Clauss, Stephanie

AU - Du, Yansheng

AU - March, Keith L.

AU - Jones, Kathryn

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ?47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treatment could ameliorate neuromuscular junction (NMJ) disruption. Objective: To determine whether pre-symptom administration of ASC-CM prevents early NMJ disconnection. Methods:We confirmed the NMJ denervation time course in mSOD1G93A mice using co-labeling of neurofilament and postsynaptic acetylcholine receptors (AchR) by -bungarotoxin. We determined whether ASC-CM ameliorates early NMJ loss in mSOD1G93A mice by systemically administering 200l ASC-CM or vehicle medium daily from post-natal days 35 to 47 and quantifying intact NMJs through co-labeling of neurofilament and synaptophysin with -bungarotoxin in gastrocnemius muscle. Results: Intact NMJs were significantly decreased in 47 day old mSOD1G93A mice (p < 0.05), and daily systemic ASC-CM prevented disease-induced NMJ denervation compared to vehicle treated mice (p < 0.05). Conclusions: Our results lay the foundation for testing the long-term neurological benefits of systemic ASC-CM therapy in the mSOD1G93A mouse model of ALS.

AB - Background: Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ?47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treatment could ameliorate neuromuscular junction (NMJ) disruption. Objective: To determine whether pre-symptom administration of ASC-CM prevents early NMJ disconnection. Methods:We confirmed the NMJ denervation time course in mSOD1G93A mice using co-labeling of neurofilament and postsynaptic acetylcholine receptors (AchR) by -bungarotoxin. We determined whether ASC-CM ameliorates early NMJ loss in mSOD1G93A mice by systemically administering 200l ASC-CM or vehicle medium daily from post-natal days 35 to 47 and quantifying intact NMJs through co-labeling of neurofilament and synaptophysin with -bungarotoxin in gastrocnemius muscle. Results: Intact NMJs were significantly decreased in 47 day old mSOD1G93A mice (p < 0.05), and daily systemic ASC-CM prevented disease-induced NMJ denervation compared to vehicle treated mice (p < 0.05). Conclusions: Our results lay the foundation for testing the long-term neurological benefits of systemic ASC-CM therapy in the mSOD1G93A mouse model of ALS.

KW - adipose-derived stem cells

KW - ALS

KW - Amyotrophic lateral sclerosis

KW - conditioned medium

KW - neuromuscular junctions

UR - http://www.scopus.com/inward/record.url?scp=85054344664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054344664&partnerID=8YFLogxK

U2 - 10.3233/RNN-180820

DO - 10.3233/RNN-180820

M3 - Article

C2 - 30010155

AN - SCOPUS:85054344664

VL - 36

SP - 621

EP - 627

JO - Restorative Neurology and Neuroscience

JF - Restorative Neurology and Neuroscience

SN - 0922-6028

IS - 5

ER -