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

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 c...

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Main Authors: 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
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2022-03-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X21003558
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author 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
author_facet 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
author_sort Jiamin Zhong
collection DOAJ
description 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.
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spelling doaj.art-e92b4b28c82a4cf2aaf8540bb5bb80d12024-04-16T15:40:36ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-03-019523540Reversibly immortalized keratinocytes (iKera) facilitate re-epithelization and skin wound healing: Potential applications in cell-based skin tissue engineeringJiamin Zhong0Hao Wang1Ke Yang2Huifeng Wang3Chongwen Duan4Na Ni5Liqin An6Yetao Luo7Piao Zhao8Yannian Gou9Shiyan Sheng10Deyao Shi11Connie Chen12William Wagstaff13Bryce Hendren-Santiago14Rex C. Haydon15Hue H. Luu16Russell R. Reid17Sherwin H. Ho18Guillermo A. Ameer19Le Shen20Tong-Chuan He21Jiaming Fan22Ministry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, ChinaMinistry 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, USAMolecular 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, ChinaBiomedical Engineering Department, Northwestern University, Evanston, IL, 60208, USABiomedical Engineering Department, Northwestern University, Evanston, IL, 60208, USAMinistry 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, USAMinistry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, ChinaMinistry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, ChinaMinistry 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, USAMinistry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, ChinaMinistry of Education Key Laboratory of Diagnostic Medicine, And Department of Clinical Biochemistry, School of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, ChinaMolecular 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, ChinaMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USAMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USAMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USAMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USAMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USAMolecular 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, USAMolecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, 60637, USABiomedical 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, USAMolecular 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, USAMolecular 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, USAMinistry 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.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.http://www.sciencedirect.com/science/article/pii/S2452199X21003558KeratinocytesSkin tissue engineeringReversible immortalizationSV40 large T antigenPPCNSkin wound healing
spellingShingle 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
Reversibly immortalized keratinocytes (iKera) facilitate re-epithelization and skin wound healing: Potential applications in cell-based skin tissue engineering
Bioactive Materials
Keratinocytes
Skin tissue engineering
Reversible immortalization
SV40 large T antigen
PPCN
Skin wound healing
title Reversibly immortalized keratinocytes (iKera) facilitate re-epithelization and skin wound healing: Potential applications in cell-based skin tissue engineering
title_full Reversibly immortalized keratinocytes (iKera) facilitate re-epithelization and skin wound healing: Potential applications in cell-based skin tissue engineering
title_fullStr Reversibly immortalized keratinocytes (iKera) facilitate re-epithelization and skin wound healing: Potential applications in cell-based skin tissue engineering
title_full_unstemmed Reversibly immortalized keratinocytes (iKera) facilitate re-epithelization and skin wound healing: Potential applications in cell-based skin tissue engineering
title_short Reversibly immortalized keratinocytes (iKera) facilitate re-epithelization and skin wound healing: Potential applications in cell-based skin tissue engineering
title_sort reversibly immortalized keratinocytes ikera facilitate re epithelization and skin wound healing potential applications in cell based skin tissue engineering
topic Keratinocytes
Skin tissue engineering
Reversible immortalization
SV40 large T antigen
PPCN
Skin wound healing
url http://www.sciencedirect.com/science/article/pii/S2452199X21003558
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