title: Amniotic fluid stem cells provide considerable advantages in epidermal regeneration: B7H4 creates a moderate inflammation microenvironment to promote wound repair.
abstract: The current treatments for severe skin injury all involve skin grafting. However, there is a worldwide shortage of donor skin tissue. In this study, we examined the advantages of using human amniotic fluid stem (hAFS) cells in skin wound healing. In vitro, hAFS cells differentiate into keratinocytes (termed hAFS-K). Like keratinocytes, hAFS-K cells express the markers K5, K14, K10 and involucrin; display typical cellular structure, including a tonofibril-rich cytoplasm; and construct a completely pluristratified epithelium in 3D culture. In vivo, in a mouse excisional wound model, GFP-positive hAFS cells participate in wound repair. Co-localization of GFP/K14 and GFP/K10 in the repaired epidermis demonstrated that hAFS cells can differentiate into keratinocytes. Real-time PCR results confirmed that hAFS cells can initiate and promote early-stage repair of skin damage. During wound repair, hAFS cells did not directly secrete repair-related factors, such as bFGF, VEGF, CXCL12, TGF-β1 and KGF, and provided a moderate inflammation reaction with lower expression of IL-1β, IL-6, TNF-α, Cox2 and Mac3. In hAFS cells, the negative co-stimulatory molecule B7H4 regulates low immunogenicity, which can provide a modest inflammatory reaction microenvironment for wound repair. Furthermore, with their uniquely high proliferation rate, hAFS cells offer a promising alternative for epidermal regeneration.
authors.affiliation: 1] The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (the State Key Laboratory Incubation Base), Soochow University, Suzhou, Jiangsu Province, P.R. China [2] Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.affiliation: 1] The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (the State Key Laboratory Incubation Base), Soochow University, Suzhou, Jiangsu Province, P.R. China [2] Department of Human Anatomy, Histology and Embryology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu Province,P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Chen
authors.affiliation: Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Yan-Zheng
authors.initials: YZ
authors.lastname: Gu
authors.affiliation: Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu Province,P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1] The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (the State Key Laboratory Incubation Base), Soochow University, Suzhou, Jiangsu Province, P.R. China [2] Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Han-Si
authors.initials: HS
authors.lastname: Liang
authors.affiliation: 1] The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (the State Key Laboratory Incubation Base), Soochow University, Suzhou, Jiangsu Province, P.R. China [2] Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Xin-Ran
authors.initials: XR
authors.lastname: You
authors.affiliation: Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Ding
authors.affiliation: Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Yun-Liang
authors.initials: YL
authors.lastname: Wang
authors.affiliation: 1] The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (the State Key Laboratory Incubation Base), Soochow University, Suzhou, Jiangsu Province, P.R. China [2] Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Ming-De
authors.initials: MD
authors.lastname: Qin
authors.affiliation: 1] The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (the State Key Laboratory Incubation Base), Soochow University, Suzhou, Jiangsu Province, P.R. China [2] Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Xue-Guang
authors.initials: XG
authors.lastname: Zhang
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D060833:Cellular Microenvironment; D004817:Epidermis / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000648:ultrastructure; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000378:metabolism*; D014945:Wound Healing; D055815:Young Adult
chemical_list: D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; D049452:Green Fluorescent Proteins