title: Exploiting human CD34+ stem cell-conditioned medium for tissue repair.
abstract: Despite the progress in our understanding of genes essential for stem cell regulation and development, little is known about the factors secreted by stem cells and their effect on tissue regeneration. In particular, the factors secreted by human CD34+ cells remain to be elucidated. We have approached this challenge by performing a cytokine/growth factor microarray analysis of secreted soluble factors in medium conditioned by adherent human CD34+ cells. Thirty-two abundantly secreted factors have been identified, all of which are associated with cell proliferation, survival, tissue repair, and wound healing. The cultured CD34+ cells expressed known stem cell genes such as Nanog, Oct4, Sox2, c-kit, and HoxB4. The conditioned medium containing the secreted factors prevented cell death in liver cells exposed to liver toxin in vitro via inhibition of the caspase-3 signaling pathway. More importantly, in vivo studies using animal models of liver damage demonstrated that injection of the conditioned medium could repair damaged liver tissue (significant reduction in the necroinflammatory activity), as well as enable the animals to survive. Thus, we demonstrate that medium conditioned by human CD34+ cells has the potential for therapeutic repair of damaged tissue in vivo.
authors.affiliation: 1] Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK [2] Qatar Biomedical Research Institute, Education City, Doha, Qatar.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mintz
authors.affiliation: 1] Department of Surgery & Hepatitis Research Center, National Taiwan University Hospital, Taipei City, Taiwan [2] Graduate Institute of Clinical Medicine, National Taiwan University, Taipei City, Taiwan.
authors.forename: Kai-Wen
authors.initials: KW
authors.lastname: Huang
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Vikash
authors.initials: V
authors.lastname: Reebye
authors.affiliation: Department of Haematology, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Georgios
authors.initials: G
authors.lastname: Nteliopoulos
authors.affiliation: 1] Department of Surgery & Hepatitis Research Center, National Taiwan University Hospital, Taipei City, Taiwan [2] Graduate Institute of Clinical Medicine, National Taiwan University, Taipei City, Taiwan.
authors.forename: Hong-Shiee
authors.initials: HS
authors.lastname: Lai
authors.affiliation: 1] Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway [2] Department of Computer and Information Science, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Pal
authors.initials: P
authors.lastname: Sætrom
authors.affiliation: Department of Medicine, UCLA School of Medicine, Los Angeles, California, USA.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kasahara
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Steen
authors.initials: S
authors.lastname: Jensen
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Madhava
authors.initials: M
authors.lastname: Pai
authors.affiliation: Department of Haematology, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Myrtle Y A
authors.initials: MY
authors.lastname: Gordon
authors.affiliation: Department of Haematology, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Marley
authors.affiliation: Department of Haematology, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Behan
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Spalding
authors.affiliation: Qatar Biomedical Research Institute, Education City, Doha, Qatar.
authors.forename: Abdelali
authors.initials: A
authors.lastname: Haoudi
authors.affiliation: 1] Qatar Biomedical Research Institute, Education City, Doha, Qatar [2] Department of Virology, School of Veterinary Medicine, Cairo University, Cairo, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Emara
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Nicholls
authors.affiliation: Division of Molecular Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Rossi
authors.affiliation: Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Nagy A
authors.initials: NA
authors.lastname: Habib
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D061251:Primary Cell Culture; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D051381:Rats; D012038:Regeneration / Q000187:drug effects*; D059467:Transcriptome; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D016207:Cytokines