Adipose-derived Stem Cell Conditioned Media Extends Survival time of a mouse model of Amyotrophic Lateral Sclerosis

Christine V. Fontanilla, Huiying Gu, Qingpeng Liu, Timothy Z. Zhu, Changwei Zhou, Brian H. Johnstone, Keith L. March, Robert M. Pascuzzi, Martin R. Farlow, Yansheng Du

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Abstract

Adipose stromal cells (ASC) secrete various trophic factors that assist in the protection of neurons in a variety of neuronal death models. In this study, we tested the effects of human ASC conditional medium (ASC-CM) in human amyotrophic lateral sclerosis (ALS) transgenic mouse model expressing mutant superoxide dismutase (SOD1 G93A). Treating symptomatic SOD1 G93A mice with ASC-CM significantly increased post-onset survival time and lifespan. Moreover, SOD1 G93A mice given ASC-CM treatment showed high motor neuron counts, less activation of microglia and astrocytes at an early symptomatic stage in the spinal cords under immunohistochemical analysis. SOD1 G93A mice treated with ASC-CM for 7 days showed reduced levels of phosphorylated p38 (pp38) in the spinal cord, a mitogen-activated protein kinase that is involved in both inflammation and neuronal death. Additionally, the levels of α-II spectrin in spinal cords were also inhibited in SOD1 G93A mice treated with ASC-CM for 3 days. Interestingly, nerve growth factor (NGF), a neurotrophic factor found in ASC-CM, played a significant role in the protection of neurodegeneration inSOD1 G93A mouse. These results indicate that ASC-CM has the potential to develop into a novel and effective therapeutic treatment for ALS.

Original languageEnglish (US)
Article number16953
JournalScientific reports
Volume5
DOIs
StatePublished - Nov 20 2015

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