Adipose-derived stem cell exosomes alleviate pathology of amyotrophic lateral sclerosis in vitro

Lee, Mijung; Ban, Jae Jun; Kim, Ki Yoon; Jeon, Gun Sang; Im, Wooseok; Sung, Jung Joon; Kim, Manho

doi:10.1016/j.bbrc.2016.09.069

Cited by 125 publications

(97 citation statements)

References 42 publications

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“…Moreover, the SOD1 mice given ASC‐CondM treatment showed, at an early symptomatic stage, high motor neuron counts and less activation of microglia and astrocytes . Similarly, exosomes from ASC alleviated the aggregation of SOD1, in neuronal cells isolated from the SOD1 mice .…”

Section: Introductionmentioning

confidence: 87%

A Combination of Intrathecal and Intramuscular Application of Human Mesenchymal Stem Cells Partly Reduces the Activation of Necroptosis in the Spinal Cord of SOD1G93A Rats

Rehorova

Vargova

Forostyak

et al. 2019

Stem Cells Translational Medicine

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An increasing number of studies have demonstrated the beneficial effects of human mesenchymal stem cells (hMSC) in the treatment of amyotrophic lateral sclerosis (ALS). We compared the effect of repeated intrathecal applications of hMSC or their conditioned medium (CondM) using lumbar puncture or injection into the muscle ( quadriceps femoris ), or a combination of both applications in symptomatic SOD1 G93A rats. We further assessed the effect of the treatment on three major cell death pathways (necroptosis, apoptosis, and autophagy) in the spinal cord tissue. All the animals were behaviorally tested (grip strength test, Basso Beattie Bresnahan (BBB) test, and rotarod), and the tissue was analyzed immunohistochemically, by qPCR and Western blot. All symptomatic SOD1 rats treated with hMSC had a significantly increased lifespan, improved motor activity and reduced number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells. Moreover, a combined hMSC delivery increased motor neuron survival, maintained neuromuscular junctions in quadriceps femoris and substantially reduced the levels of proteins involved in necroptosis (Rip1, mixed lineage kinase‐like protein, cl‐casp8), apoptosis (cl‐casp 9) and autophagy (beclin 1). Furthermore, astrogliosis and elevated levels of Connexin 43 were decreased after combined hMSC treatment. The repeated application of CondM, or intramuscular injections alone, improved motor activity; however, this improvement was not supported by changes at the molecular level. Our results provide new evidence that a combination of repeated intrathecal and intramuscular hMSC applications protects motor neurons and neuromuscular junctions, not only through a reduction of apoptosis and autophagy but also through the necroptosis pathway, which is significantly involved in cell death in rodent SOD1 G93A model of ALS. stem cells translational medicine 2019;8:535–547

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Section: Introductionmentioning

confidence: 87%

A Combination of Intrathecal and Intramuscular Application of Human Mesenchymal Stem Cells Partly Reduces the Activation of Necroptosis in the Spinal Cord of SOD1G93A Rats

Rehorova

Vargova

Forostyak

et al. 2019

Stem Cells Translational Medicine

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“…Accumulating evidence indicates that exosomes derived from ADSCs have the ability to treat various diseases, including diabetes ( Zhao et al, 2018 ), stress urinary incontinence ( Ni et al, 2018 ), amyotrophic lateral sclerosis ( Lee et al, 2016 ), and ischemia/reperfusion injuries ( Pu et al, 2017 ). To examine their effect on a model of ischemic injury, we isolated primary ADSCs from C57/Bl6 mice.…”

Section: Resultsmentioning

confidence: 99%

Exosomes Derived From CircAkap7-Modified Adipose-Derived Mesenchymal Stem Cells Protect Against Cerebral Ischemic Injury

Jiang

et al. 2020

Front. Cell Dev. Biol.

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Background Cerebral ischemic injury is a complicated pathological process. Adipose-derived stromal cells (ADSCs) have been used as a therapeutic strategy, with their therapeutic effects chiefly attributed to paracrine action rather than trans- differentiation. Studies have shown that circAkap7 was found to be downregulated in a mouse model of transient middle cerebral artery occlusion (tMCAO). Methods To explore whether exosomes derived from circAkap7-modified ADSCs (exo-circAkap7) have therapeutic effects on cerebral ischemic injury, a mouse model of tMCAO, as well as an in vitro model of oxygen and glucose deprivation-reoxygenation (OGD-R) in primary astrocytes, were used. Results Results showed that treatment with exo-circAkap7 protected against tMCAO in mice, and in vitro experiments confirmed that co-culture with exo-circAkap7 attenuated OGD-R-induced cellular injury by absorbing miR-155-5p, promoting ATG12-mediated autophagy, and inhibiting NRF2-mediated oxidative stress. Conclusion We demonstrate here that exo-circAkap7 protected against cerebral ischemic injury by promoting autophagy and ameliorating oxidative stress.

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“…This finding strongly indicates that ADSC-EVs could be potentially useful in treatment of Alzheimer's disease. According to the results of other study focusing on cultured primary brain cells from G93A mice carrying ALS phenotype, EVs from ADSC were capable to reduce level of harmful SOD1 aggregates in such neural cells and upregulate levels of phosphorylated cAMP response element-binding protein (p-CREB) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-the mitochondrial proteins, which are decreased during ALS development and progression [47]. Similarly, Bonafede and colleagues have shown in their study on ALS model in vitro, that ADSC-EVs provided neuroprotective effect and increased viability of motorneuron-like cell line NSC-3 subjected to cytotoxic hydrogen peroxide inducing cells apoptosis, suggesting antioxidative mechanism of EVs action [48].…”

Section: Neurological Diseasesmentioning

confidence: 99%

Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review

Lelek

Zuba‐Surma

2020

IJMS

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Mesenchymal stem/ stromal cells (MSCs) represent progenitor cells of various origin with multiple differentiation potential, representing the most studied population of stem cells in both in vivo pre-clinical and clinical studies. MSCs may be found in many tissue sources including extensively studied adipose tissue (ADSCs) and umbilical cord Wharton’s jelly (UC-MSCs). Most of sanative effects of MSCs are due to their paracrine activity, which includes also release of extracellular vesicles (EVs). EVs are small, round cellular derivatives carrying lipids, proteins, and nucleic acids including various classes of RNAs. Due to several advantages of EVs when compare to their parental cells, MSC-derived EVs are currently drawing attention of several laboratories as potential new tools in tissue repair. This review focuses on pro-regenerative properties of EVs derived from ADSCs and UC-MSCs. We provide a synthetic summary of research conducted in vitro and in vivo by employing animal models and within initial clinical trials focusing on neurological, cardiovascular, liver, kidney, and skin diseases. The summarized studies provide encouraging evidence about MSC-EVs pro-regenerative capacity in various models of diseases, mediated by several mechanisms. Although, direct molecular mechanisms of MSC-EV action are still under investigation, the current growing data strongly indicates their potential future usefulness for tissue repair.

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Adipose-derived stem cell exosomes alleviate pathology of amyotrophic lateral sclerosis in vitro

Cited by 125 publications

References 42 publications

A Combination of Intrathecal and Intramuscular Application of Human Mesenchymal Stem Cells Partly Reduces the Activation of Necroptosis in the Spinal Cord of SOD1G93A Rats

A Combination of Intrathecal and Intramuscular Application of Human Mesenchymal Stem Cells Partly Reduces the Activation of Necroptosis in the Spinal Cord of SOD1G93A Rats

Exosomes Derived From CircAkap7-Modified Adipose-Derived Mesenchymal Stem Cells Protect Against Cerebral Ischemic Injury

Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review

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