Key Takeaways & Executive Findings
- •• Adenovirus-mediated overexpression of CCR7 in BMSCs was successfully achieved, with significantly upregulated CCR7 protein and mRNA levels. • CCR7-BMSCs exhibited excellent cytocompatibility when co-cultured with porcine small intestinal submucosa (SIS) membrane. • The CCR7-BMSCs-SIS composite significantly accelerated wound closure in a rat skin defect model compared to SIS alone. • The composite enhanced angiogenesis, as evidenced by increased expression of VEGF, CD31, and PCNA in wound tissue.
Abstract
BACKGROUND: The clinical outcomes of autologous and allogeneic skin transplants, which are commonly used for repairing skin lesions, are often suboptimal. In recent years, advancements in tissue engineering have provided new hope for skin repair. Nevertheless, the regeneration of blood vessels within skin tissue engineering remains a significant challenge. Porcine small intestinal submucosa and bone marrow-derived mesenchymal stem cells are widely utilized natural extracellular matrix biomaterials and seed cells in current tissue engineering research. Chemokine receptor 7 is a cytokine that can promote angiogenesis. OBJECTIVE: To observe the repair effect and angiogenesis ability of chemokine receptor 7-bone marrow mesenchymal stem cells-porcine small intestinal submucosa membrane on rat back skin damage. METHODS: (1) The adenovirus vector overexpressing chemokine receptor 7 was used to transfect bone marrow mesenchymal stem cells. The transfection efficiency was evaluated using western blot assay and RT-qPCR. (2) The bone marrow mesenchymal stem cells overexpressing chemokine receptor 7 were co-cultured with porcine small intestinal submucosa. Cytocompatibility was assessed through scanning electron microscopy and live/dead cell staining. (3) 12 SD rats were utilized to establish a skin defect animal experimental model, and chemokine receptor 7-bone marrow mesenchymal stem cells-porcine small intestinal submucosa (experimental group) and porcine small intestinal submucosa alone (control group) were applied to the skin defects. Wound healing was observed at 1, 3, 7, and 14 days post-modeling. At 7 and 14 days, western blot was used to detect vascular endothelial growth factor protein expression in wound healing tissue, and immunohistochemical staining was used to detect CD31 and proliferating cell nuclear antigen protein expression. RESULTS AND CONCLUSION: (1) Adenovirus-mediated overexpression of chemokine receptor 7 in bone marrow mesenchymal stem cells was successfully constructed. The protein and mRNA expression of chemokine receptor 7 in the transfection group was significantly upregulated compared with the control and empty vector groups (P < 0.001). (2) Scanning electron microscopy and live/dead cell staining showed that bone marrow mesenchymal stem cells overexpressing chemokine receptor 7 grew well on the porcine small intestinal submucosa membrane, indicating good cytocompatibility. (3) Compared with the control group, the wound area in the experimental group was significantly reduced (P < 0.05), and the protein expression of vascular endothelial growth factor, CD31, and proliferating cell nuclear antigen in the wound healing tissue was higher than that in the control group (P < 0.05), indicating that the chemokine receptor 7-bone marrow mesenchymal stem cells-porcine small intestinal submucosa membrane had a strong ability to promote wound angiogenesis.
1. Introduction
The skin is one of the important organs of the human body to defend against external damage. At present, the demand for skin repair is increasing among patients with various skin diseases such as diabetic and radiation ulcers, as well as skin defects caused by burns, trauma, scars, and tumor resection [1-2]. In clinical treatment, skin grafting is the most widely used method. Autologous skin grafting has the advantages of good histocompatibility and low immune rejection, but for patients with large-area skin defects, the limited area of autologous skin available for transplantation is a common dilemma, and it may lead to scar formation and secondary infection at the donor site, affecting the patient's appearance and quality of life. Allogeneic skin grafting can partially solve the problem of insufficient autologous skin sources, but patients may face severe immune rejection, as well as an increased risk of infection with other diseases due to immunosuppression, posing a potential threat to the patient's health [3-4].
The development of tissue engineering has brought new hope for skin repair and transplantation. Skin tissue engineering is a frontier interdisciplinary field that combines cell biology, engineering, and materials science. The main content is to seed seed cells with specific differentiation functions cultured in vitro onto biocompatible scaffold materials. The seed cells can adhere, grow, proliferate, and differentiate on the scaffold, ultimately forming tissue-engineered skin with similar structure and function to natural skin, which can replace damaged tissue and achieve comprehensive reconstruction of skin function [5-6]. Porcine small intestinal submucosa (SIS) is a natural extracellular matrix biomaterial rich in collagen, fibronectin, glycosaminoglycans, and proteoglycans. It has good cytocompatibility, antimicrobial activity, and the ability to promote tissue-specific regeneration. Bone marrow mesenchymal stem cells (BMSCs) are widely used as seed cells in tissue engineering due to their multi-lineage differentiation potential and immunomodulatory properties. However, vascular regeneration within skin tissue engineering remains a major challenge. Chemokine receptor 7 (CCR7) is a cytokine that can promote angiogenesis. This study aims to investigate the effect of CCR7-BMSCs combined with SIS on skin repair and angiogenesis in a rat model.
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Fan Meirong, Li Guangqi, Song Xumei, Yan Xin, Sui Ruizhi (2026). Chemokine receptor 7-bone marrow mesenchymal stem cells combined with porcine small intestinal submucosa promote skin repair in rats. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21206
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Frequently Asked Questions
What is the role of chemokine receptor 7 (CCR7) in skin repair?
CCR7 is a cytokine that promotes angiogenesis, which is crucial for wound healing. In this study, overexpression of CCR7 in bone marrow mesenchymal stem cells enhanced the angiogenic capacity of the composite scaffold, leading to improved skin repair.
How were bone marrow mesenchymal stem cells (BMSCs) modified in this study?
BMSCs were transfected with an adenovirus vector overexpressing CCR7. The transfection efficiency was confirmed by Western blot and RT-qPCR, showing significantly increased CCR7 expression.
What is the significance of using porcine small intestinal submucosa (SIS) in skin tissue engineering?
SIS is a natural extracellular matrix biomaterial that provides a supportive scaffold for cell attachment and growth. It has good cytocompatibility and promotes tissue regeneration, making it an ideal scaffold for skin tissue engineering.
What were the main findings of the animal study?
In a rat skin defect model, the CCR7-BMSCs-SIS composite significantly accelerated wound closure and increased the expression of angiogenesis markers (VEGF, CD31, and PCNA) compared to SIS alone, indicating enhanced wound healing and angiogenesis.
What are the potential clinical applications of this research?
This research suggests that CCR7-BMSCs combined with SIS could be developed as a bioactive scaffold for skin repair, particularly for large or chronic wounds where vascularization is a challenge. It may offer a promising approach for tissue-engineered skin substitutes.
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