Systemic dental pulp stem cell secretome therapy in a mouse model of amyotrophic lateral sclerosis

Junmei Wang, Kirstin Zuzzio, Chandler Walker

Research output: Contribution to journalArticle

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron (MN) disease with no cure. Accumulating evidence indicates ALS involves a complex interaction between central glia and the peripheral immune response and neuromuscular interface. Stem cell secretomes contain various beneficial trophic factors and cytokines, and we recently demonstrated that administration of the secretome of adipose-derived stem cells (ASCs) during early neuromuscular junction (NMJ) denervation in the mutant superoxide dismutase (mSOD1G93A) ALS mouse ameliorated NMJ disruption. In the present study, we hypothesized that administration of dental pulp stem cell secretome in the form of conditioned medium (DPSC-CM) at different stages of disease would promote NMJ innervation, prevent MN loss and extend lifespan. Our findings show that DPSC-CM significantly improved NMJ innervation at postnatal day (PD) 47 compared to vehicle treated mSOD1G93A mice (p < 0.05). During late pre-symptomatic stages (PD70-P91), DPSC-CM significantly increased MN survival (p < 0.01) and NMJ preservation (p < 0.05), while reactive gliosis in the ventral horn remained unaffected. For DPSC-CM treated mSOD1G93A mice beginning at symptom onset, post-onset days of survival as well as overall lifespan was significantly increased compared to vehicle treated mice (p < 0.05). This is the first study to show therapeutic benefits of systemic DPSC secretome in experimental ALS, and establishes a foundation for future research into the treatment effects and mechanistic analyses of DPSC and other stem cell secretome therapies in ALS.

Original languageEnglish (US)
Article number165
JournalBrain Sciences
Volume9
Issue number7
DOIs
StatePublished - Jul 1 2019

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Dental Pulp
Amyotrophic Lateral Sclerosis
Cell- and Tissue-Based Therapy
Neuromuscular Junction
Stem Cells
Conditioned Culture Medium
Motor Neurons
Motor Neuron Disease
Gliosis
Denervation
Horns
Neuroglia
Superoxide Dismutase
Cytokines
Therapeutics

Keywords

  • ALS
  • Amyotrophic lateral sclerosis
  • Conditioned medium
  • Dental pulp stem cells
  • DPSC
  • Secretome

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Systemic dental pulp stem cell secretome therapy in a mouse model of amyotrophic lateral sclerosis. / Wang, Junmei; Zuzzio, Kirstin; Walker, Chandler.

In: Brain Sciences, Vol. 9, No. 7, 165, 01.07.2019.

Research output: Contribution to journalArticle

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