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Updated: Aug 5, 2025
Creation and Transplantation of an Adipose-derived Stem Cell ASC Sheet in a Diabetic Wound-healing Model
Published on: August 4, 2017
dCas9-Based PDGFR-β Activation ADSCs Accelerate Wound Healing in Diabetic Mice through Angiogenesis and ECM
Yumeng Li1, Deyong Li1, Lu You1
1Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Abstract:
The chronic wound represents a serious disease characterized by a failure to heal damaged skin and surrounding soft tissue. Mesenchymal stem cells (MSCs) derived from adipose tissue (ADSCs) are a promising therapeutic strategy, but their heterogeneity may result in varying or insufficient therapeutic capabilities. In this study, we discovered that all ADSCs populations expressed platelet-derived growth factor receptor β (PDGFR-β), while the expression level decreased dynamically with passages. Thus, using a CRISPRa-based system, we endogenously overexpressed PDGFR-β in ADSCs. Moreover, a series of in vivo and in vitro experiments were conducted to determine the functional changes in PDGFR-β activation ADSCs (AC-ADSCs) and to investigate the underlying mechanisms. With the activation of PDGFR-β, AC-ADSCs exhibited enhanced migration, survival, and paracrine capacity relative to control ADSCs (CON-ADSCs). In addition, the secretion components of AC-ADSCs contained more pro-angiogenic factors and extracellular matrix-associated molecules, which promoted the function of endothelial cells (ECs) in vitro. Additionally, in in vivo transplantation experiments, the AC-ADSCs transplantation group demonstrated improved wound healing rates, stronger collagen deposition, and angiogenesis. Consequently, our findings revealed that PDGFR-β overexpression enhanced the migration, survival, and paracrine capacity of ADSCs and improved therapeutic effects after transplantation to diabetic mice.
Insights
Overexpressing platelet-derived growth factor receptor β (PDGFR-β) in adipose-derived stem cells (ADSCs) enhances their therapeutic potential for chronic wounds. Activated ADSCs show improved migration, survival, and promote better wound healing in diabetic mice.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Wound Healing Research
Background:
- Chronic wounds pose a significant health challenge due to impaired healing.
- Adipose-derived stem cells (ADSCs) show therapeutic promise but exhibit heterogeneity.
- Platelet-derived growth factor receptor β (PDGFR-β) expression decreases with ADSC passages.
Purpose of the Study:
- To enhance ADSC therapeutic capabilities by overexpressing PDGFR-β.
- To investigate the functional and mechanistic changes in PDGFR-β activated ADSCs (AC-ADSCs).
- To evaluate the efficacy of AC-ADSCs in promoting chronic wound healing.
Main Methods:
- Utilized a CRISPRa system for endogenous PDGFR-β overexpression in ADSCs.
- Conducted in vitro assays to assess migration, survival, and paracrine function.
- Performed in vivo transplantation studies in diabetic mice models for wound healing assessment.
Main Results:
- AC-ADSCs demonstrated significantly enhanced migration, survival, and paracrine capacity compared to control ADSCs (CON-ADSCs).
- AC-ADSC secretions promoted endothelial cell function with increased pro-angiogenic and extracellular matrix factors.
- In vivo studies showed accelerated wound healing, increased collagen deposition, and improved angiogenesis in AC-ADSC treated groups.
Conclusions:
- PDGFR-β overexpression is a viable strategy to improve ADSC function for regenerative therapies.
- AC-ADSCs exhibit superior therapeutic potential for chronic wound healing, particularly in diabetic models.
- Enhanced migration, survival, and paracrine signaling underlie the improved efficacy of AC-ADSCs.
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