IDR-1018 induces cell proliferation, migration, and reparative gene expression in 2D culture and 3D human skin equivalents
Thuany Alencar-Silva
Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil
Search for more papers by this authorRobert Pogue
Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil
Search for more papers by this authorFelipe Saldanha-Araujo
Laboratório de Hematologia, Departamento de Ciências da Saúde, Universidade de Brasília, Brasilia, Brazil
Programa de Pós-graduação em Patologia Molecular, Universidade de Brasília, Brasília, Brazil
Search for more papers by this authorSimoni Campos Dias
Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil
Pós-Graduação em Biologia Animal, Universidade de Brasília, Campus Darcy Ribeiro, Brasília, Brazil
Search for more papers by this authorOctavio Luiz Franco
Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil
S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil
Programa de Pós-graduação em Patologia Molecular, Universidade de Brasília, Brasília, Brazil
Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, Brazil
Search for more papers by this authorCorresponding Author
Juliana Lott Carvalho
Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil
OneSkin Technologies, San Francisco, CA, USA
Faculdade de Medicina, Universidade de Brasília, Brasilia, Brazil
Correspondence
Juliana Lott Carvalho, Faculdade de Medicina, Universidade de Brasília, Brasilia, DF, Brazil.
Email: [email protected]
Search for more papers by this authorThuany Alencar-Silva
Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil
Search for more papers by this authorRobert Pogue
Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil
Search for more papers by this authorFelipe Saldanha-Araujo
Laboratório de Hematologia, Departamento de Ciências da Saúde, Universidade de Brasília, Brasilia, Brazil
Programa de Pós-graduação em Patologia Molecular, Universidade de Brasília, Brasília, Brazil
Search for more papers by this authorSimoni Campos Dias
Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil
Pós-Graduação em Biologia Animal, Universidade de Brasília, Campus Darcy Ribeiro, Brasília, Brazil
Search for more papers by this authorOctavio Luiz Franco
Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil
S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil
Programa de Pós-graduação em Patologia Molecular, Universidade de Brasília, Brasília, Brazil
Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, Brazil
Search for more papers by this authorCorresponding Author
Juliana Lott Carvalho
Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brazil
OneSkin Technologies, San Francisco, CA, USA
Faculdade de Medicina, Universidade de Brasília, Brasilia, Brazil
Correspondence
Juliana Lott Carvalho, Faculdade de Medicina, Universidade de Brasília, Brasilia, DF, Brazil.
Email: [email protected]
Search for more papers by this authorAbstract
Skin lesions are associated with functional/cosmetic problems for those afflicted. Scarless regeneration is a challenge, not limited to the skin, and focus of active investigation. Recently, the host defense peptide innate defense regulatory peptide 1018 (IDR-1018) has shown exciting regenerative properties. Nevertheless, literature regarding IDR-1018 regenerative potential is scarce and limited to animal models. Here, we evaluated the regenerative potential of IDR-1018 using human 2D and 3D human skin equivalents. First, we investigated IDR-1018 using human cells found in skin—primary fibroblasts, primary keratinocytes, and the MeWo melanocytes cell line. IDR-1018 promoted cell proliferation and expression of marker of proliferation Ki-67, matrix metalloproteinase 1, and hyaluronan synthase 2 by fibroblasts. In keratinocytes, a drastic increase in expression was observed for Ki-67, matrix metalloproteinase 1, C-X-C motif chemokine receptor type 4, C-X-C motif chemokine receptor type 7, fibroblast growth factor 2, hyaluronan synthase 2, vascular endothelial growth factor, and elastin, reflecting an intense stimulation of these cells. In melanocytes, increased migration and proliferation were observed following IDR-1018 treatment. The capacity of IDR-1018 to promote dermal contraction was verified using a dermal model. Finally, using a 3D human skin equivalent lesion model, we revealed that the regenerative potential of IDR1018, previously tested in mice and pigs, is valid for human skin tissue. Lesions closed faster in IDR-1018-treated samples, and the gene expression signature observed in 2D was reproduced in the 3D human skin equivalents. Overall, the present data show the regenerative potential of IDR-1018 in an experimental system comprising human cells, underscoring the potential application for clinical investigation.
CONFLICT OF INTEREST
Authors declare no conflict of interest. A. Z., D. F., M. G., and J. L. C. are collaborators and/or scientific advisors for OneSkin Technologies.
Supporting Information
| Filename | Description |
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| TERM_2953-Supp_0001_T1-T3.pdfPDF document, 58.3 KB |
Table S1. Primers and Probes Table S2. qRT-PCR data in different skin cell types cultured as monolayers Table S3. qRT-PCR data of human skin equivalents (containing both epidermis and dermis layers). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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