title: Integrin-binding elastin-like polypeptide as an in situ gelling delivery matrix enhances the therapeutic efficacy of adipose stem cells in healing full-thickness cutaneous wounds.
abstract: One crucial issue in stem cell therapy used for tissue repair is often the lack of selective carriers to deliver stem cells to the site of injury where the native extracellular matrix is pathologically damaged or lost. Therefore, it is necessary to develop a biomaterial that is permissive to stem cells and is suitable to replace injured or missing matrix. The major aim of this study is to investigate the potential of an RGD-containing elastin-like polypeptide (REP) with the structure TGPG[VGRGD(VGVPG)6]20WPC to engraft adipose stem cells (ASC) to full-thickness excisional wounds in mice. We implanted REP into the wound defects via body temperature-induced in situ aggregation. Engrafted REP exhibited a half-life of 2.6days in the wounds and did not elicit any pathological immune responses. REP itself significantly accelerated wound closure and reepithelialization and upregulated the expression of dermal tissue components. A combined administration of REP and ASC formed a hydrogel-like ASC/REP composite, which provided better neovascularization than the use of ASCs alone and increased the viability of transplanted ASC, improving overall wound healing. In vitro and in vivo mechanistic investigations suggested that REP enhances ASC survival at least in part via the Fak/Src adhesion-induced upregulation of Mek/Erk and PI3K/Akt survival pathways. We conclude that REP is a promising therapeutic agent for the improvement of stem cell-based therapy for enhanced tissue regeneration and repair.
authors.affiliation: Laboratory of Biochemistry and Cellular Engineering, Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea.
authors.forename: Seong-Kyoon
authors.initials: SK
authors.lastname: Choi
authors.affiliation: Laboratory of Biochemistry and Cellular Engineering, Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea; Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Park
authors.affiliation: Laboratory of Biochemistry and Cellular Engineering, Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Laboratory of Biochemistry and Cellular Engineering, Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea.
authors.forename: Kyeong-Min
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Laboratory of Biochemistry and Cellular Engineering, Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea; Faculty Affiliation to Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea.
authors.forename: Enjoo
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Republic of Korea.
authors.forename: Kyu-Shik
authors.initials: KS
authors.lastname: Jeong
authors.affiliation: Laboratory of Biochemistry and Cellular Engineering, Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea; Faculty Affiliation to Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea; Faculty Affiliation to Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea. Electronic address: wbjeon@dgist.ac.kr.
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Jeon
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002478:Cells, Cultured; D004549:Elastin / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D016023:Integrins / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D012867:Skin / Q000473:pathology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D016023:Integrins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D004549:Elastin
keywords: Adipose stem cells; Angiogenesis; Elastin-like polypeptide; Signal transduction; Stem cell survival; Wound healing