Reversibly immortalized keratinocytes(iKera)facilitate re-epithelization and skin wound healing:Potential applications in cell-based skin tissue engineering  

作　　者：Jiamin Zhong Hao Wang Ke Yang Huifeng Wang Chongwen Duan Na Ni Liqin An Yetao Luo Piao Zhao Yannian Gou Shiyan Sheng Deyao Shi Connie Chen William Wagstaff b Bryce Hendren-Santiago b Rex C.Haydon b Hue H.Luu b Russell R.Reid Sherwin HHo Guillermo A.Ameer Le Shen Tong-Chuan He Jiaming Fan 

机构地区：[1]Ministry of Education Key Laboratory of Diagnostic Medicine,And Department of Clinical Biochemistry,School of Laboratory Medicine,Chongqing Medical University,Chongqing,400016,China [2]Molecular Oncology Laboratory,Department of Orthopaedic Surgery and Rehabilitation Medicine,The University of Chicago Medical Center,Chicago,IL,60637,USA [3]The Pediatric Research Institute,The Children’s Hospital of Chongqing Medical University,Chongqing,400014,China [4]Biomedical Engineering Department,Northwestern University,Evanston,IL,60208,USA [5]Department of Orthopaedics,Union Hospital of Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [6]Department of Surgery,The University of Chicago Medical Center,Chicago,IL,60637,USA [7]Center for Advanced Regenerative Engineering(CARE),Evanston,IL,60208,USA [8]Department of Surgery,Northwestern University Feinberg School of Medicine,Chicago,IL,60616,USA

出　　处：《Bioactive Materials》2022年第3期523-540,共18页生物活性材料（英文）

基　　金：The reported study was supported in part by research grants from the 2019 Chongqing Support Program for Entrepreneurship and Innovation(No.cx2019113)(JF);the 2019 Science and Technology Research Plan Project of Chongqing Education Commission(KJQN201900410)(JF);the 2019 Youth Innovative Talent Training Program of Chongqing Education Commission(No.CY200409)(JF);the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)(JF)and the National Key Research and Development Program of China(2016YFC1000803);RRR,TCH and GAA were partially funded by the National Institutes of Health(DE030480);WW was supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281);This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599);the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430;TCH was also supported by the Mabel Green Myers Research Endowment Fund,The University of Chicago Orthopaedics Alumni Fund,and The University of Chicago SHOCK Fund.Funding sources were not involved in the study design;in the collection,analysis and/or interpretation of data;in the writing of the report;or in the decision to submit the paper for publication.

摘　　要：Skin injury is repaired through a multi-phase wound healing process of tissue granulation and re-epithelialization.Any failure in the healing process may lead to chronic non-healing wounds or abnormal scar formation.Although significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical challenge.Keratinocytes are critical to re-epithelialization and wound healing.Here,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound healing.We first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were non-tumorigenic.In a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound model.Thus,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.

关 键 词：KERATINOCYTES Skin tissue engineering Reversible immortalization SV40 large T antigen PPCN Skin wound healing 

分 类 号：R318.08[医药卫生—生物医学工程] R64[医药卫生—基础医学]