title: Conditioned medium derived from umbilical cord mesenchymal stem cells regenerates atrophied muscles.
abstract: We investigated the regenerative effects and regulatory mechanisms of human umbilical cord mesenchymal stem cells (UC-MSCs)-derived conditioned medium (CM) in atrophied muscles using an in vivo model. To determine the appropriate harvest point of UC-CM, active factor content was analyzed in the secretome over time. A muscle atrophy model was induced in rats by hindlimb suspension (HS) for 2 weeks. Next, UC-CM was injected directly into the soleus muscle of both hind legs to assess its regenerative efficacy on atrophy-related factors after 1 week of HS. During HS, muscle mass and muscle fiber size were significantly reduced by over 2-fold relative to untreated controls. Lactate accumulation within the muscles was similarly increased. By contrast, all of the above analytical factors were significantly improved in HS-induced rats by UC-CM injection compared with saline injection. Furthermore, the expression levels of desmin and skeletal muscle actin were significantly elevated by UC-CM treatment. Importantly, UC-CM effectively suppressed expression of the atrophy-related ubiquitin E3-ligases, muscle ring finger 1 and muscle atrophy F-box by 2.3- and 2.1-fold, respectively. UC-CM exerted its actions by stimulating the phosphoinositol-3-kinase (PI3K)/Akt signaling cascade. These findings suggest that UC-CM provides an effective stimulus to recover muscle status and function in atrophied muscles.
authors.affiliation: Department of Biotechnology, CHA University, Seongnam, Republic of Korea.
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, CHA University, Seongnam, Republic of Korea.
authors.forename: Z-Hun
authors.initials: ZH
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, CHA University, Seongnam, Republic of Korea.
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, CHA University, Seongnam, Republic of Korea. Electronic address: yschoi@cha.ac.kr.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Choi
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D012038:Regeneration; D044843:SKP Cullin F-Box Protein Ligases / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D000070584:Tripartite Motif Proteins / Q000096:biosynthesis; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases
keywords: Conditioned medium; Muscle atrophy; Phosphoinositol-3-kinase (PI3K)/Akt pathway; Secretome; Umbilical cord mesenchymal stem cell