title: Hypoxic conditioned medium from mesenchymal stem cells promotes lymphangiogenesis by regulation of mitochondrial-related proteins.
abstract: BACKGROUND
  Recently, cell-based therapeutic lymphangiogenesis has emerged and provided hope for lymphatic regeneration. Previous studies have demonstrated that secretomes of mesenchymal stem cells (MSCs) facilitate the regeneration of various damaged tissues. This study was conducted to evaluate the lymphangiogenic potential of hypoxic conditioned media (HCM) from MSCs.
  
  
  METHODS
  To investigate the effects of MSC-secreted factors in starved human lymphatic endothelial cells (hLEC), hLECs were treated with endothelial basal medium (EBM)-2 (control), normoxic conditioned media (NCM), or HCM in vitro and in vivo.
  
  
  RESULTS
  MSCs expressed lymphangiogenic factors including EGF, FGF2, HGF, IGF-1, and VEGF-A and -C. hLECs were treated with each medium. hLEC proliferation, migration, and tube formation were improved under HCM compared with NCM. Moreover, expression of mitochondrial-related factors, MFN1and 2, were improved in HCM-treated hLECs. Lymphedema mice injected with HCM showed markedly decreased lymphedema via increased lymphatic vessel formation when compared with EBM-2- or NCM-treated mice.
  
  
  CONCLUSIONS
  This study suggested that HCM from MSCs contain high levels of secreted lymphangiogenic factors and promote lymphangiogenesis by regulating mitochondrial-related factors. Thus, treatment with HCM may be a therapeutic strategy for lymphedema.
authors.affiliation: Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, Seoul, 03722, Republic of Korea.
authors.forename: Chang Youn
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Rehabilitation Medicine, National Traffic Injury Rehabilitation Hospital, College of Medicine, The Catholic University of Korea, Yangpyeong-gun, 12564, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kang
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, 25601, Gangwon-do, Republic of Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Lim
authors.affiliation: Catholic Kwandong University International St. Mary's Hospital, Incheon Metropolitan City, 22711, Republic of Korea.
authors.forename: Onju
authors.initials: O
authors.lastname: Ham
authors.affiliation: Department of Biology Education, College of Education, Pusan National University, Busan, 46241, Republic of Korea. wchang1975@pusan.ac.kr.
authors.forename: Woochul
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Rehabilitation Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Dongsu-ro 56, Bupyeong-gu, Incheon, 21431, Republic of Korea. dhjangmd@naver.com.
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Jang
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000737:chemistry; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D024101:Mitochondrial Proteins / Q000502:physiology*; D012038:Regeneration
chemical_list: D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned; D024101:Mitochondrial Proteins
keywords: Hypoxic conditioned media; Lymphangiogenesis; Lymphatic endothelial cells; Mesenchymal stem cells; Mitochondrial-related protein