title: Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1.
abstract: The role of Wharton's jelly-derived human mesenchymal stem cells (WJ-MSCs) in inhibiting muscle cell death has been elucidated in this study. Apoptosis induced by serum deprivation in mouse skeletal myoblast cell lines (C2C12) was significantly reduced when the cell lines were cocultured with WJ-MSCs. Antibody arrays indicated high levels of chemokine (C motif) ligand (XCL1) secretion by cocultured WJ-MSCs and XCL1 protein treatment resulted in complete inhibition of apoptosis in serum-starved C2C12 cells. Apoptosis of C2C12 cells and loss of differentiated C2C12 myotubes induced by lovastatin, another muscle cell death inducer, was also inhibited by XCL1 treatment. However, XCL1 treatment did not inhibit apoptosis of cell lines other than C2C12. When XCL1-siRNA pretreated WJ-MSCs were cocultured with serum-starved C2C12 cells, apoptosis was not inhibited, thus confirming that XCL1 is a key factor in preventing C2C12 cell apoptosis. We demonstrated the therapeutic effect of XCL1 on the zebrafish myopathy model, generated by knock down of a causative gene ADSSL1. Furthermore, the treatment of XCL1 resulted in significant recovery of the zebrafish skeletal muscle defects. These results suggest that human WJ-MSCs and XCL1 protein may act as promising and novel therapeutic agents for treatment of myopathies and other skeletal muscle diseases.
authors.affiliation: Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: SooJin
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Ki
authors.affiliation: Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.|Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Sang Eon
authors.initials: SE
authors.lastname: Park
authors.affiliation: Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Min-Jeong
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Hyung
authors.affiliation: Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.|Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Na Kyung
authors.initials: NK
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sangmi
authors.initials: S
authors.lastname: Shim
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.|Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.|Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D019744:Chemokines, C / Q000378:metabolism*; D018920:Coculture Techniques; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D020543:Proteome; D040901:Proteomics / Q000379:methods; D059631:Wharton Jelly / Q000166:cytology*; D015027:Zebrafish
chemical_list: D019744:Chemokines, C; D020543:Proteome; C092390:XCL1 protein, human; D008148:Lovastatin