Related Experiment Video
Updated: May 2, 2026
Protocol to Create Chronic Wounds in Diabetic Mice
Published on: September 25, 2019
MCC950 promotes diabetic wound healing through modulating macrophage polarization in an MDSC-dependent manner
Wei Yan1, Tianyi Ni1, Qian Zhang2
1Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu, PR China.
Abstract:
Diabetic foot ulcers (DFUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Currently, there is a lack of effective therapeutic strategies. MCC950, a highly selective nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor, has been reported to show strong anti-inflammation effects in many diseases. In this study, we unveiled the role of MCC950 in DFU mice model and its underlying molecular mechanisms. MCC950 could significantly accelerate diabetic wound healing, as shown by shortened healing time and better healing quality. Moreover, increased M2 phenotype macrophages and decreased pro-inflammatory genes were observed in MCC950-treated DFU mice. Additionally, myeloid-derived suppressor cells (MDSCs) were significantly increased in blood, spleen and wound tissues at different time courses. Specifically, MCC950 could recruit more MDSCs in an early phase in DFU mice, exerting an anti-inflammation effect. We identified the cell crosstalk between macrophages and MDSCs with MCC950 treatment process. Depleting MDSCs in vivo could eliminate the therapeutic effect of MCC950 on diabetic wound healing through inhibiting M2 macrophage polarization. Besides, MDSCs isolated from the wounds of MCC950 or saline treated mice were cocultured with bone marrow derived macrophage (BMDM) in a transwell system. Results confirmed that MDSCs sorted from MCC950 treated mice caused a significant increased percentage of M2 macrophages. Collectively, our findings suggest that the administration of MCC950 has the potential to accelerate diabetic wound healing by promoting M2 macrophage polarization in an MDSC-dependent manner. This study provides valuable insights into the utilization of pharmacological agents for DFU treatment.
Insights
MCC950 accelerates diabetic foot ulcer healing by reducing inflammation and promoting M2 macrophages via myeloid-derived suppressor cells (MDSCs). This drug enhances wound healing quality and speed in diabetic mice.
Area of Science:
- Biomedical Science
- Immunology
- Wound Healing Research
Background:
- Diabetic foot ulcers (DFUs) present a significant clinical challenge due to stalled inflammatory phases in wound healing.
- Current therapeutic strategies for DFUs are limited, necessitating novel treatment approaches.
Purpose of the Study:
- To investigate the therapeutic potential of MCC950, a nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor, in a diabetic foot ulcer (DFU) mouse model.
- To elucidate the underlying molecular mechanisms of MCC950 in accelerating diabetic wound healing.
Main Methods:
- Administration of MCC950 to a DFU mouse model.
- Assessment of wound healing progression, including healing time and quality.
- Analysis of macrophage polarization (M1/M2 phenotypes) and gene expression profiles.
- Quantification of myeloid-derived suppressor cells (MDSCs) in blood, spleen, and wound tissues.
- In vivo MDSC depletion and in vitro co-culture experiments with bone marrow-derived macrophages (BMDMs).
Main Results:
- MCC950 significantly accelerated diabetic wound healing and improved healing quality.
- MCC950 treatment led to increased M2 phenotype macrophages and decreased pro-inflammatory gene expression.
- Significant increases in MDSCs were observed in various tissues following MCC950 administration.
- MDSCs were found to be crucial for MCC950's therapeutic effect, mediating M2 macrophage polarization.
Conclusions:
- MCC950 effectively promotes diabetic wound healing by enhancing M2 macrophage polarization in an MDSC-dependent manner.
- The findings highlight MCC950 as a promising pharmacological agent for DFU treatment.
- This study elucidates a novel therapeutic pathway involving MCC950, MDSCs, and macrophages for DFU management.
