Bioactive Materials (Mar 2022)
Reversibly immortalized keratinocytes (iKera) facilitate re-epithelization and skin wound healing: Potential applications in cell-based skin tissue engineering
- 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,
- Bryce Hendren-Santiago,
- Rex C. Haydon,
- Hue H. Luu,
- Russell R. Reid,
- Sherwin H. Ho,
- Guillermo A. Ameer,
- Le Shen,
- Tong-Chuan He,
- Jiaming Fan
Affiliations
- Jiamin Zhong
- Ministry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
- Hao Wang
- Ministry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA
- Ke Yang
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA; The Pediatric Research Institute, The Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
- Huifeng Wang
- Biomedical Engineering Department, Northwestern University, Evanston, IL, 60208, USA
- Chongwen Duan
- Biomedical Engineering Department, Northwestern University, Evanston, IL, 60208, USA
- Na Ni
- Ministry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA
- Liqin An
- Ministry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
- Yetao Luo
- Ministry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
- Piao Zhao
- Ministry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA
- Yannian Gou
- Ministry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
- Shiyan Sheng
- Ministry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
- Deyao Shi
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA; Department of Orthopaedics, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Connie Chen
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA
- William Wagstaff
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA
- Bryce Hendren-Santiago
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA
- Rex C. Haydon
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA
- Hue H. Luu
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA
- Russell R. Reid
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA; Department of Surgery, The University of Chicago Medical Center, Chicago, IL, 60637, USA; Center for Advanced Regenerative Engineering (CARE), Evanston, IL, 60208, USA
- Sherwin H. Ho
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA
- Guillermo A. Ameer
- Biomedical Engineering Department, Northwestern University, Evanston, IL, 60208, USA; Center for Advanced Regenerative Engineering (CARE), Evanston, IL, 60208, USA; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60616, USA
- Le Shen
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA; Department of Surgery, The University of Chicago Medical Center, Chicago, IL, 60637, USA
- Tong-Chuan He
- Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA; Department of Surgery, The University of Chicago Medical Center, Chicago, IL, 60637, USA; Center for Advanced Regenerative Engineering (CARE), Evanston, IL, 60208, USA
- Jiaming Fan
- Ministry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USA; Corresponding author. Ministry of Education Key Laboratory of Diagnostic Medicine, Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
- Journal volume & issue
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Vol. 9
pp. 523 – 540
Abstract
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.
