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Platelet-derived growth factor and stromal cell-derived factor-1 promote the skin wound repairing effect of bone mesenchymal stem cells: a key role of matrix metalloproteinase 1 and collagens.

ABSTRACT: Bone marrow mesenchymal stem cells (BMSCs) have been applied to treatment of skin wounds. In the current study, the effect of BMSCs on secretion of several cytokines during skin wound healing was investigated. In addition, the mechanism underlying the promoting effect of platelet-derived growth factor (PDGF) and stromal cell-derived factor-1 (SDF-1) on BMSCs was also preliminarily explored. BMSCs were isolated from femur and tibia of rats and characterized by surface antibodies. Skin wounded rats was employed as the in vivo model for evaluating the effect of BMSCs on skin healing and secretion of basic fibroblast growth factor (bFGF), interleukin 1? (IL-1?), PDGF, SDF-1, and tumor necrosis factor ? (TNF-?). The promoting effect of SDF-1 and PDGF on the function of BMSCs was also assessed by focusing on the activity of matrix metalloproteinase 1 (MMP-1) signaling and deposition of collagens. Administration of BMSCs promoted skin wound healing and induced the production of bFGF, IL-1?, PDGF, SDF-1, and TNF-?. Moreover, PDGF treatment recruited BSMCs to injured sites and strengthened the effect of BMSCs on skin wound by suppressing activity of MMP-1. Similarly, SDF-1 treatment also increased the treating effect of BMSCs on skin injury, which was through the deposition of collagen I and collagen III. Both indicators exerted their effect on BMSCs in a dose-dependent manner. Findings outlined in the current study indicated that administration of BMSCs accelerated wound healing and enhanced the production of PDGF and SDF-1, which would contribute to recruitment of BMSCs in injured area and deposition of collagens.

SUBMITTER: Xu H

PROVIDER: S-EPMC6965411 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Platelet-derived growth factor and stromal cell-derived factor-1 promote the skin wound repairing effect of bone mesenchymal stem cells: a key role of matrix metalloproteinase 1 and collagens.

Xu Hailong H Zhang Hui H Ding Yue Y

International journal of clinical and experimental pathology 20170801 8

Bone marrow mesenchymal stem cells (BMSCs) have been applied to treatment of skin wounds. In the current study, the effect of BMSCs on secretion of several cytokines during skin wound healing was investigated. In addition, the mechanism underlying the promoting effect of platelet-derived growth factor (PDGF) and stromal cell-derived factor-1 (SDF-1) on BMSCs was also preliminarily explored. BMSCs were isolated from femur and tibia of rats and characterized by surface antibodies. Skin wounded rat ...[more]

PMID: 31966676

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Project description:BackgroundChronic radiation dermatitis (CRD) is a late consequence of radiation with high incidence in patients receiving radiotherapy. Conventional therapies often yield unsatisfactory results. Therefore, this study aimed to explore the therapeutic potential and mechanism of adipose-derived stem cells (ADSCs) for CRD, paving the way for novel regenerative therapies in clinical practice.MethodsClinical CRD skin biopsies were analyzed to character the pathological changes of CRD skin and guided the animal modeling scheme. Subsequently, an in vivo analysisusing mouse CRD models was conducted to explore their effects of ADSCs on CRD, monitoring therapeutic impact for up to 8 weeks. Transcriptome sequencing and histologic sections analysis were performed to explore the potential therapeutic mechanism of ADSCs. Following observing extensive apoptosis of transplanted ADSCs, the therapeutic effect of ADSCs were compared with those of apoptosis-inhibited ADSCs. Multiphoton imaging and analysis of collagen morphologic features were employed to explain how translated ADSCs promote collagen remodeling at the microscopic level based on the contrast of morphology of collagen fibers.ResultsFollowing injection into CRD-afflicted skin, ADSCs therapy effectively mitigated symptoms of CRD, including acanthosis of the epidermis, fibrosis, and irregular collagen deposition, consistent with the possible therapeutic mechanism suggested by transcriptome sequencing. Notably, in vivo tracking revealed a significant reduction in ADSCs number due to extensive apoptosis. Inhibiting apoptosis in ADSCs partially tempered their therapeutic effects. Mechanically, analysis of collagen morphologic features indicated that translated ADSCs might promote dermal extracellular matrix remodeling through enlarging, lengthening, crimping, and evening collagen, counteracting the atrophy and rupture caused by irradiation.ConclusionsThis study demonstrated that ADSCs underwent substantial apoptosis upon local skin transplantation, and paradoxically, this apoptosis is essential for their efficacy in promoting the regeneration of late radiation-impaired skin. Mechanically, transplanted ADSCs could promote the remodeling and rearrangement of radiation-damaged dermal collagen matrix.

Project description:Skin injuries are frequently encountered in daily life, but deep wounds often poorly self-heal and do not recover completely. In this study, we propose a novel skin patch that combines antibiotic, cell-derived extracellular matrix (ECM) and biocompatible polyvinyl alcohol (PVA) hydrogel. Methods: Decellularized human lung fibroblast-derived matrix (hFDM) was prepared on tissue culture plate (TCP) and PVA solution was then poured onto it. After a freeze-thaw process, PVA was peeled off from TCP along with hFDM tightly anchored to PVA. Subsequently, ciprofloxacin (Cipro)-incorporated PVA/hFDM (PVA/Cipro/hFDM) was fabricated via diffusion-based drug loading. Results: In vitro analyses of PVA/Cipro/hFDM show little cytotoxicity of ciprofloxacin, stability of hFDM, rich fibronectin in hFDM, and good cell attachment, respectively. In addition, hFDM proved to be beneficial in promoting cell migration of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs) using transwell inserts. The antibacterial drug Cipro was very effective in suppressing colony growth of gram-negative and -positive bacteria as identified via an inhibition zone assay. For animal study, infected wound models in BALB/c mice were prepared and four test groups (control, PVA, PVA/Cipro, PVA/Cipro/hFDM) were administered separately and their effect on wound healing was examined for up to 21 days. The results support that Cipro successfully reduced bacterial infection and thus encouraged faster wound closure. Further analysis using histology and immunofluorescence revealed that the most advanced skin regeneration was achieved with PVA/Cipro/hFDM, as assessed via re-epithelialization, collagen texture and distribution in the epidermis, and skin adnexa (i.e., glands and hair follicles) regeneration in the dermis. Conclusion: This work demonstrates that our skin patch successfully consolidates the regenerative potential of ECM and the antibacterial activity of Cipro for advanced wound healing.

Dataset Information

Platelet-derived growth factor and stromal cell-derived factor-1 promote the skin wound repairing effect of bone mesenchymal stem cells: a key role of matrix metalloproteinase 1 and collagens.

Publications

Platelet-derived growth factor and stromal cell-derived factor-1 promote the skin wound repairing effect of bone mesenchymal stem cells: a key role of matrix metalloproteinase 1 and collagens.

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