International Journal of Molecular Sciences

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Special Issue Editors

Dr. Sujeong Jang

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Guest Editor

Department of Physiology, Chonnam National University Medical School, Hwasun, Jellanam-do 58128, Republic of Korea
Interests: mesenchymal stem cell; neroscience; ischemic spinal cord injury; neuronal differentiation; epigenesis; Wnt; exosome; sport genetics

Prof. Dr. Han Seong Jeong

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Guest Editor

Department of Physiology, Chonnam National University Medical School, Hwasun, Jellanam-do 58128, Republic of Korea
Interests: mesenchymal stem cell; neuroscience; Alzheimer’s disease; Parkinson’s disease; neuronal differentiation; exosome; neurodegenerative disease; electrophysiology

Special Issue Information

Dear Colleagues,

Stem cell-based therapies for repair and regeneration show a paradigm shift; however, stem cell therapy to treat neurodegenerative disease has not been as successful as expected in some preclinical studies. Due to this, many groups have studied whether the therapeutic effect of mesenchymal stem cells (MSCs) is due to the cell type, microenvironment after transplant, or disease model. Recent studies suggest that the stem cell-conditioned medium, secretome, or exosome appear to protect from cell death in neurodegenerative diseases. MSCs are able to cross the blood–brain barrier. However, in vivo MSC treatment has risks related to cell differentiation and their tumorigenic potential, and the consequent failure to reach the target site or reach the injured site in the brain is negligible. Evidence confirms that neuroprotection of MSC occurs due to its secretion of different proteins, including growth factors, cytokines, chemokines, metabolites, and bioactive lipids, which have paracrine and autocrine therapeutic activities. The secretome/conditioned medium from MSC is a heterogeneous bioactive molecule considered a biotechnological product, which is safer compared to the living MSC. The secretome directly contributes to the recovery of the damaged tissues. Therefore, considering their regenerative and restorative abilities, the secretome/exosome from different sources of MSC is proposed as the main biological effector as a possible alternative to MSC treatment in neurodegenerative diseases.

Dr. Sujeong Jang
Prof. Dr. Han Seong Jeong
Guest Editors

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Keywords

neurodegenerative disease
mesenchymal stem cell
exosome
therapy
conditioned medium
secretome

Published Papers (2 papers)

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Research

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21 pages, 10435 KiB

Open AccessArticle

Neuroprotective Effects of the Neural-Induced Adipose-Derived Stem Cell Secretome against Rotenone-Induced Mitochondrial and Endoplasmic Reticulum Dysfunction

by Mahesh Ramalingam, Sujeong Jang, Jinsu Hwang, Boeun Kim, Hyong-Ho Cho, Eungpil Kim and Han-Seong Jeong

Int. J. Mol. Sci. 2023, 24(6), 5622; https://doi.org/10.3390/ijms24065622 - 15 Mar 2023

Cited by 3 | Viewed by 2383

Abstract

Mesenchymal stem cells (MSCs) have therapeutic effects on neurodegenerative diseases (NDDs) known by their secreted molecules, referred to as the “secretome”. The mitochondrial complex I inhibitor, rotenone (ROT), reproduces α-synuclein (α-syn) aggregation seen in Parkinson’s disease (PD). In this present study, we examined the neuroprotective effects of the secretome from neural-induced human adipose tissue-derived stem cells (NI-ADSC-SM) during ROT toxicity in SH-SY5Y cells. Exposure to ROT significantly impaired the mitophagy by increased LRRK2, mitochondrial fission, and endoplasmic reticulum (ER) stress (ERS). ROT also increased the levels of calcium (Ca²⁺), VDAC, and GRP75, and decreased phosphorylated (p)-IP3R Ser1756/total (t)-IP3R1. However, NI-ADSC-SM treatment decreased Ca²⁺ levels along with LRRK2, insoluble ubiquitin, mitochondrial fission by halting p-DRP1 Ser616, ERS by reducing p-PERK Thr981, p-/t-IRE1α, p-SAPK, ATF4, and CHOP. In addition, NI-ADSC-SM restored the mitophagy, mitochondrial fusion, and tethering to the ER. These data suggest that NI-ADSC-SM decreases ROT-induced dysfunction in mitochondria and the ER, which subsequently stabilized tethering in mitochondria-associated membranes in SH-SY5Y cells. Full article

(This article belongs to the Special Issue Exosome: New Approaches of Therapy for Cell Death)

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Review

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18 pages, 781 KiB

Open AccessReview

Therapeutic Application of Extracellular Vesicles-Capsulated Adeno-Associated Virus Vector via nSMase2/Smpd3, Satellite, and Immune Cells in Duchenne Muscular Dystrophy

by Yasunari Matsuzaka, Yukihiko Hirai, Kazuo Hashido and Takashi Okada

Int. J. Mol. Sci. 2022, 23(3), 1551; https://doi.org/10.3390/ijms23031551 - 28 Jan 2022

Cited by 5 | Viewed by 4032

Abstract

Duchenne muscular dystrophy (DMD) is caused by loss-of-function mutations in the dystrophin gene on chromosome Xp21. Disruption of the dystrophin–glycoprotein complex (DGC) on the cell membrane causes cytosolic Ca²⁺ influx, resulting in protease activation, mitochondrial dysfunction, and progressive myofiber degeneration, leading to muscle wasting and fragility. In addition to the function of dystrophin in the structural integrity of myofibers, a novel function of asymmetric cell division in muscular stem cells (satellite cells) has been reported. Therefore, it has been suggested that myofiber instability may not be the only cause of dystrophic degeneration, but rather that the phenotype might be caused by multiple factors, including stem cell and myofiber functions. Furthermore, it has been focused functional regulation of satellite cells by intracellular communication of extracellular vesicles (EVs) in DMD pathology. Recently, a novel molecular mechanism of DMD pathogenesis—circulating RNA molecules—has been revealed through the study of target pathways modulated by the Neutral sphingomyelinase2/Neutral sphingomyelinase3 (nSMase2/Smpd3) protein. In addition, adeno-associated virus (AAV) has been clinically applied for DMD therapy owing to the safety and long-term expression of transduction genes. Furthermore, the EV-capsulated AAV vector (EV-AAV) has been shown to be a useful tool for the intervention of DMD, because of the high efficacy of the transgene and avoidance of neutralizing antibodies. Thus, we review application of AAV and EV-AAV vectors for DMD as novel therapeutic strategy. Full article

(This article belongs to the Special Issue Exosome: New Approaches of Therapy for Cell Death)

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