Bone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model
Abstract Background Hypertrophic scars (HSs) are formed via an aberrant response to the wound healing process. HSs can be cosmetic or can result in functional problems. Prolonged proliferation and remodeling phases disrupt wound healing, leading to excessive collagen production and HS formation. How...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1383-x |
| _version_ | 1819072236014796800 |
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| author | Ching-Hsuan Hu Yi-Wen Tseng Chih-Yung Chiou Kuan-Chun Lan Chih-Hung Chou Chun-San Tai Hsien-Da Huang Chiung-Wen Hu Ko-Hsun Liao Shiow-Shuh Chuang Jui-Yung Yang Oscar K. Lee |
| author_facet | Ching-Hsuan Hu Yi-Wen Tseng Chih-Yung Chiou Kuan-Chun Lan Chih-Hung Chou Chun-San Tai Hsien-Da Huang Chiung-Wen Hu Ko-Hsun Liao Shiow-Shuh Chuang Jui-Yung Yang Oscar K. Lee |
| author_sort | Ching-Hsuan Hu |
| collection | DOAJ |
| description | Abstract Background Hypertrophic scars (HSs) are formed via an aberrant response to the wound healing process. HSs can be cosmetic or can result in functional problems. Prolonged proliferation and remodeling phases disrupt wound healing, leading to excessive collagen production and HS formation. However, there are currently no satisfactory drugs to prevent HS formation. Mesenchymal stem cell (MSC) conditioned medium (CM) has therapeutic effects on wound healing and preventing HS formation. Bone marrow concentrate (BMC) contains various growth factors and cytokines that are crucial for regeneration and has been applied in the clinical setting. In this study, we evaluated the effects of BMC-induced MSC CM on HS formation in a rabbit ear model. Methods We established a rabbit ear wound model by generating full-thickness wounds in the ears of rabbits (n = 12) and treated wounds with MSC CM, BMC CM, or BMC-induced MSC CM. Dermal fibroblasts from human hypertrophic scar were stimulated with transforming growth factor beta 1 (TGF-β1) for 24 h and cultured in each culture medium for 72 h. We measured the hypertrophic scar (HS) formation during the skin regeneration by measuring the expression of several remodeling molecules and the effect of these conditioned media on active human HS fibroblasts. Results Our results showed that BMC-induced MSC CM had greater antifibrotic effects than MSC CM and BMC CM significantly attenuated HS formation in rabbits. BMC-induced MSC CM accelerated wound re-epithelization by increasing cell proliferation. Additionally, BMC-induced MSC CM also inhibited fibrosis by decreasing profibrotic gene and protein expression, promoting extracellular matrix turnover, inhibiting fibroblast contraction, and reversing myofibroblast activation. Conclusions BMC-induced MSC CM modulated the proliferation and remodeling phases of wound healing, representing a potential wound healing agent and approach for preventing HS formation. |
| first_indexed | 2024-12-21T17:34:31Z |
| format | Article |
| id | doaj.art-b6d2e435a99243a5bc17dbefb873acd0 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-21T17:34:31Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
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| series | Stem Cell Research & Therapy |
| spelling | doaj.art-b6d2e435a99243a5bc17dbefb873acd02022-12-21T18:55:49ZengBMCStem Cell Research & Therapy1757-65122019-08-0110111310.1186/s13287-019-1383-xBone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear modelChing-Hsuan Hu0Yi-Wen Tseng1Chih-Yung Chiou2Kuan-Chun Lan3Chih-Hung Chou4Chun-San Tai5Hsien-Da Huang6Chiung-Wen Hu7Ko-Hsun Liao8Shiow-Shuh Chuang9Jui-Yung Yang10Oscar K. Lee11Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung UniversityDepartment of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung UniversityInstitute of Clinical Medicine, National Yang-Ming UniversityInstitute of Molecular Medicine and Bioengineering, National Chiao Tung UniversityDepartment of Biological Science and Technology, Center for Intelligent Drug Systems and Smart Bio-devices (IDS²B), National Chiao Tung UniversityDepartment of Biological Science and Technology, National Chiao Tung UniversityWarshel Institute for Computational Biology, School of Life and Health Sciences, School of Sciences and Engineering, The Chinese University of Hong KongDepartment of Public Health, Chung Shan Medical UniversityInstitute of Clinical Medicine, National Yang-Ming UniversityDepartment of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung UniversityDepartment of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung Medical College and Chang Gung UniversityInstitute of Clinical Medicine, National Yang-Ming UniversityAbstract Background Hypertrophic scars (HSs) are formed via an aberrant response to the wound healing process. HSs can be cosmetic or can result in functional problems. Prolonged proliferation and remodeling phases disrupt wound healing, leading to excessive collagen production and HS formation. However, there are currently no satisfactory drugs to prevent HS formation. Mesenchymal stem cell (MSC) conditioned medium (CM) has therapeutic effects on wound healing and preventing HS formation. Bone marrow concentrate (BMC) contains various growth factors and cytokines that are crucial for regeneration and has been applied in the clinical setting. In this study, we evaluated the effects of BMC-induced MSC CM on HS formation in a rabbit ear model. Methods We established a rabbit ear wound model by generating full-thickness wounds in the ears of rabbits (n = 12) and treated wounds with MSC CM, BMC CM, or BMC-induced MSC CM. Dermal fibroblasts from human hypertrophic scar were stimulated with transforming growth factor beta 1 (TGF-β1) for 24 h and cultured in each culture medium for 72 h. We measured the hypertrophic scar (HS) formation during the skin regeneration by measuring the expression of several remodeling molecules and the effect of these conditioned media on active human HS fibroblasts. Results Our results showed that BMC-induced MSC CM had greater antifibrotic effects than MSC CM and BMC CM significantly attenuated HS formation in rabbits. BMC-induced MSC CM accelerated wound re-epithelization by increasing cell proliferation. Additionally, BMC-induced MSC CM also inhibited fibrosis by decreasing profibrotic gene and protein expression, promoting extracellular matrix turnover, inhibiting fibroblast contraction, and reversing myofibroblast activation. Conclusions BMC-induced MSC CM modulated the proliferation and remodeling phases of wound healing, representing a potential wound healing agent and approach for preventing HS formation.http://link.springer.com/article/10.1186/s13287-019-1383-xHypertrophic scarBone marrow concentrateMesenchymal stem cell-conditioned medium |
| spellingShingle | Ching-Hsuan Hu Yi-Wen Tseng Chih-Yung Chiou Kuan-Chun Lan Chih-Hung Chou Chun-San Tai Hsien-Da Huang Chiung-Wen Hu Ko-Hsun Liao Shiow-Shuh Chuang Jui-Yung Yang Oscar K. Lee Bone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model Stem Cell Research & Therapy Hypertrophic scar Bone marrow concentrate Mesenchymal stem cell-conditioned medium |
| title | Bone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model |
| title_full | Bone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model |
| title_fullStr | Bone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model |
| title_full_unstemmed | Bone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model |
| title_short | Bone marrow concentrate-induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model |
| title_sort | bone marrow concentrate induced mesenchymal stem cell conditioned medium facilitates wound healing and prevents hypertrophic scar formation in a rabbit ear model |
| topic | Hypertrophic scar Bone marrow concentrate Mesenchymal stem cell-conditioned medium |
| url | http://link.springer.com/article/10.1186/s13287-019-1383-x |
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