Sun Hyun Kwon1, Suk Ho Bhang2, Hyeon-Ki Jang3, Taiyoun Rhim4, Byung-Soo Kim5. 1. School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea. 2. School of Chemical Engineering, Sungkyunkwan University, Suwon, Republic of Korea. 3. Interdisciplinary Program for Bioengineering, College of Engineering, Seoul National University, Seoul, Republic of Korea. 4. Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea. Electronic address: rhim@hanyang.ac.kr. 5. School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea; Institute of Bioengineering, Institute of Chemical Processess, Seoul National University, Seoul, Republic of Korea. Electronic address: byungskim@snu.ac.kr.
Abstract
BACKGROUND: It was previously shown that human adipose-derived stromal cell (hADSC)-conditioned medium (CM) promotes wound healing. An essential part of the wound healing process is neovascularization in the wound bed. MATERIALS AND METHODS: We hypothesized that CM prepared from hADSCs cultured as spheroids in three-dimensional suspension bioreactors (spheroid CM) would contain much higher concentrations of angiogenic growth factors secreted by hADSCs, induce a higher extent of neovascularization in the wound bed, and improve wound healing as compared with CM prepared by conventional monolayer culture (monolayer CM). RESULTS: The concentrations of angiogenic growth factors (i.e., vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor) in spheroid CM were 20- to 145-fold higher than those in monolayer CM. Either fresh medium, monolayer CM, or spheroid CM was administered to full-thickness wounds created on the dorsal aspects of athymic mice. The monolayer CM promoted wound healing as compared with fresh medium or no treatment. Importantly, wound closure was faster, and dermal and epidermal regeneration was improved in the spheroid CM-treated mice compared with that in the monolayer CM-treated mice. CONCLUSIONS: The improved wound healing by spheroid CM may be attributed, at least in part, to enhanced neovascularization in the wound beds. The spheroid-based CM approach showed potential as a therapy for skin wound repair.
BACKGROUND: It was previously shown that human adipose-derived stromal cell (hADSC)-conditioned medium (CM) promotes wound healing. An essential part of the wound healing process is neovascularization in the wound bed. MATERIALS AND METHODS: We hypothesized that CM prepared from hADSCs cultured as spheroids in three-dimensional suspension bioreactors (spheroid CM) would contain much higher concentrations of angiogenic growth factors secreted by hADSCs, induce a higher extent of neovascularization in the wound bed, and improve wound healing as compared with CM prepared by conventional monolayer culture (monolayer CM). RESULTS: The concentrations of angiogenic growth factors (i.e., vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor) in spheroid CM were 20- to 145-fold higher than those in monolayer CM. Either fresh medium, monolayer CM, or spheroid CM was administered to full-thickness wounds created on the dorsal aspects of athymic mice. The monolayer CM promoted wound healing as compared with fresh medium or no treatment. Importantly, wound closure was faster, and dermal and epidermal regeneration was improved in the spheroid CM-treated mice compared with that in the monolayer CM-treated mice. CONCLUSIONS: The improved wound healing by spheroid CM may be attributed, at least in part, to enhanced neovascularization in the wound beds. The spheroid-based CM approach showed potential as a therapy for skin wound repair.