title: Spatially Assembled Bilayer Cell Sheets of Stem Cells and Endothelial Cells Using Thermosensitive Hydrogels for Therapeutic Angiogenesis.
abstract: Although the coculture of multiple cell types has been widely employed in regenerative medicine, in vivo transplantation of cocultured cells while maintaining the hierarchical structure remains challenging. Here, a spatially assembled bilayer cell sheet of human mesenchymal stem cells and human umbilical vein endothelial cells on a thermally expandable hydrogel containing fibronectin is prepared and its effect on in vitro proangiogenic functions and in vivo ischemic injury is investigated. The expansion of hydrogels in response to a temperature change from 37 to 4 °C allows rapid harvest and delivery of the bilayer cell sheet to two different targets (an in vitro model glass surface and in vivo tissue). The in vitro study confirms that the bilayer sheet significantly increases proangiogenic functions such as the release of nitric oxide and expression of vascular endothelial cell genes. In addition, transplantation of the cell sheet from the hydrogels into a hindlimb ischemia mice model demonstrates significant retardation of necrosis particularly in the group transplated with the bilayer sheet. Collectively, the bilayer cell sheet is readily transferrable from the thermally expandable hydrogel and represents an alternative approach for recovery from ischemic injury, potentially via improved cell-cell communication.
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea.|Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
authors.forename: Indong
authors.initials: I
authors.lastname: Jun
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea.|BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea.
authors.forename: Taufiq
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea.|BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea.
authors.forename: Seongwoo
authors.initials: S
authors.lastname: Bak
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea.|BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea.
authors.forename: Joong-Yup
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea.|BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea.|BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea.
authors.forename: Jinkyu
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea.|BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea.
authors.forename: Yu Bin
authors.initials: YB
authors.lastname: Lee
authors.affiliation: Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
authors.forename: Hongsoo
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
authors.forename: Hojeong
authors.initials: H
authors.lastname: Jeon
authors.affiliation: Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea.|BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea.
authors.forename: Heungsoo
authors.initials: H
authors.lastname: Shin
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D006614:Hindlimb / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology; D007150:Immunohistochemistry; D007511:Ischemia / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000502:physiology; D013696:Temperature; D023822:Tissue Engineering / Q000379:methods
chemical_list: D020100:Hydrogels
keywords: cell sheet engineering; cell-cell interaction; endothelial cells; stem cells; thermosensitive hydrogels