title: Efficacious and clinically relevant conditioned medium of human adipose-derived stem cells for therapeutic angiogenesis.
abstract: Using stem cell-conditioned medium (CM) might be a viable alternative to stem cell transplantation, which is often hampered by low grafting efficiency and potential tumorigenesis, but the concentrations of angiogenic growth factors in CM are too low for therapeutic use and some components of the medium are not for human use. We used three-dimensional (3D) spheroid culture of human adipose-derived stem cells (ADSCs) with clinically relevant medium composed of amino acids, vitamins, glucose, and human serum to produce clinically relevant CM containing angiogenic and/or antiapoptotic factors such as vascular endothelial cell growth factor, fibroblast growth factor 2, hepatocyte growth factor, and chemokine (C-X-C motif) ligand 12. The concentrations of these factors were 23- to 27-fold higher than that in CM produced by conventional monolayer culture. Compared with injection of either monolayer culture CM or human ADSC, injection of spheroid culture CM to an ischemic region in mice significantly enhanced endothelial cell growth, CD34(+)/PTPRC(-) (endothelial progenitor) cell mobilization from bone marrow, and bone marrow cell homing to the ischemic region, resulting in improved blood vessel density, limb salvage, and blood perfusion in a mouse hindlimb ischemia model. The stem cell CM developed in this study will likely be an effective alternative to conventional stem cell transplantation therapy.
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea.
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Bhang
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea.
authors.forename: Seahyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea.
authors.forename: Jung-Youn
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul, Korea.
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Lee
authors.affiliation: Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, Korea.
authors.forename: Hyeon-Ki
authors.initials: HK
authors.lastname: Jang
authors.affiliation: 1] School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea [2] Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, Korea [3] Institute of Chemical Processes, Seoul National University, Seoul, Korea.
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018929:Cell Culture Techniques; D017077:Culture Media, Conditioned; D006801:Humans; D051379:Mice; D013234:Stem Cells / Q000166:cytology*
chemical_list: D017077:Culture Media, Conditioned