Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats

Xu, Yifeng; Wu, Yan-Xiang; Wang, Hong-Mei; Gao, Cui-Hua; Xu, Yang-Yang; Yan, Yang

doi:10.1016/j.clinsp.2023.100181

Cited by 9 publications

(9 citation statements)

References 47 publications

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“…There is evidence that pyroptosis promotes diabetic complications, including diabetes-induced wound [ 26 ]. In DFU rats, bone marrow mesenchymal stem cells can promote cell proliferation and angiogenesis, reduce pyroptosis to promote wound healing [ 27 ]. The MALAT1/miR-374a-5p signaling axis can suppress pyroptosis to contribute to the healing of DFU [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer

Zheng,

Na,

Yao

et al. 2024

BMC Infect Dis

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Background Diabetic foot ulcer (DFU) is one of the main chronic complications caused by diabetes, leading to amputation in severe cases. Bacterial infection affects the wound healing in DFU. Methods DFU patients who met the criteria were selected, and the clinical data were recorded in detail. The pus exudate from the patient’s foot wound and venous blood were collected for biochemical analysis. The distribution of bacterial flora in pus exudates of patients was analyzed by 16S rRNA sequencing, and the correlation between DFU and pathogenic variables, pyroptosis and immunity was analyzed by statistical analysis. Then, the effects of key bacteria on the inflammation, proliferation, apoptosis, and pyroptosis of polymorphonuclear leukocytes were investigated by ELISA, CCK-8, flow cytometry, RT-qPCR and western blot. Results Clinical data analysis showed that Wagner score was positively correlated with the level of inflammatory factors, and there was high CD3+, CD4+, and low CD8+ levels in DFU patients with high Wagner score. Through alpha, beta diversity analysis and species composition analysis, Corynebacterium accounted for a large proportion in DFU. Logistics regression model and Person correlation analysis demonstrated that mixed bacterial infections could aggravate foot ulcer, and the number of bacteria was closely related to inflammatory factors PCT, PRT, immune cells CD8+, and pyroptosis-related proteins GSDMD and NLRP3. Through in vitro experiments, Corynebacterium inhibited cell proliferation, promoted inflammation (TNF-α, PCT, CRP), apoptosis and pyroptosis (IL-1β, LDH, IL-18, GSDMD, NLRP3, and caspase-3). Conclusion Mixed bacterial infections exacerbate DFU progression with a high predominance of Corynebacterium, and Corynebacterium promotes inflammation, apoptosis and pyroptosis to inhibit DFU healing.

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Section: Discussionmentioning

confidence: 99%

16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer

Zheng,

Na,

Yao

et al. 2024

BMC Infect Dis

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“…Inflammation may be reduced, autophagy can be enhanced, and pyroptosis can be reduced with the use of BM‐MSC‐CM, which can aid the healing of DFUs. These results bring to light a potentially life‐saving therapeutic use of BM‐MSC‐CM for the management of DFUs that sidesteps the potential hazards of live cell therapy 105 …”

Section: Stem Cell Therapymentioning

confidence: 93%

“…Furthermore, tCO2 (total carbon dioxide), ABI, magnetic resonance angiography, and painless walking time analyses all showed significantly better outcomes in those undergoing treatment with BM‐MSCs relative to those who were administered BM‐MNCs 24 weeks after therapy. These findings suggest that, in diabetic individuals suffering from critical limb ischemia, BM‐MSCs may be well tolerated as well as more efficient than BM‐MNCs in improving limb oxygenation and speeding up the healing process of foot ulcers 104 Also, Xu et al 105 demonstrated that BM‐MSC‐CM is an excellent therapy for DFU in rats with type 2 diabetes. Inflammation may be reduced, autophagy can be enhanced, and pyroptosis can be reduced with the use of BM‐MSC‐CM, which can aid the healing of DFUs.…”

Section: Stem Cell Therapymentioning

confidence: 98%

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Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review

Hetta,

Elsaghir,

Sijercic

et al. 2024

Health Science Reports

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BackgroundDiabetes has evolved into a worldwide public health issue. One of the most serious complications of diabetes is diabetic foot ulcer (DFU), which frequently creates a significant financial strain on patients and lowers their quality of life. Up until now, there has been no curative therapy for DFU, only symptomatic relief or an interruption in the disease's progression. Recent studies have focused attention on mesenchymal stem cells (MSCs), which provide innovative and potential treatment candidates for several illnesses as they can differentiate into various cell types. They are mostly extracted from the placenta, adipose tissue, umbilical cord (UC), and bone marrow (BM). Regardless of their origin, they show comparable features and small deviations. Our goal is to investigate MSCs' therapeutic effects, application obstacles, and patient benefit strategies for DFU therapy.MethodologyA comprehensive search was conducted using specific keywords relating to DFU, MSCs, and connected topics in the databases of Medline, Scopus, Web of Science, and PubMed. The main focus of the selection criteria was on English‐language literature that explored the relationship between DFU, MSCs, and related factors.Results and DiscussionNumerous studies are being conducted and have demonstrated that MSCs can induce re‐epithelialization and angiogenesis, decrease inflammation, contribute to immunological modulation, and subsequently promote DFU healing, making them a promising approach to treating DFU. This review article provides a general snapshot of DFU (including clinical presentation, risk factors and etiopathogenesis, and conventional treatment) and discusses the clinical progress of MSCs in the management of DFU, taking into consideration the side effects and challenges during the application of MSCs and how to overcome these challenges to achieve maximum benefits.ConclusionThe incorporation of MSCs in the management of DFU highlights their potential as a feasible therapeutic strategy. Establishing a comprehensive understanding of the complex relationship between DFU pathophysiology, MSC therapies, and related obstacles is essential for optimizing therapy outcomes and maximizing patient benefits.

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“…Xu et al revealed that downregulated expression level of NLRP3, GSDMD, GSDMD-N, pro-caspase-1 and pro-IL-1β proteins contributes to the impairment of wound healing in hyperglycemic rats. 81 A prominent study by Bitto and co-workers has demonstrated that NLRP3 inflammasome activation impairs the process of wound healing in diabetic mice. 9 Prior research has also demonstrated that the persistent activation of the NLRP3 inflammasome in macrophages has a detrimental effect on the process of wound repair in T2D patients and mouse models.…”

Section: Pyroptosis-dependent Signaling Pathways In the Progression O...mentioning

confidence: 99%

The Mechanism of Pyroptosis and Its Application Prospect in Diabetic Wound Healing

Al Mamun,

Shao,

Geng

et al. 2024

JIR

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Pyroptosis defines a form of pro-inflammatory-dependent programmed cell death triggered by gasdermin proteins, which creates cytoplasmic pores and promotes the activation and accumulation of immune cells by releasing several pro-inflammatory mediators and immunogenic substances upon cell rupture. Pyroptosis comprises canonical (mediated by Caspase-1) and non-canonical (mediated by Caspase-4/5/11) molecular signaling pathways. Numerous studies have explored the contributory roles of inflammasome and pyroptosis in the progression of multiple pathological conditions such as tumors, nerve injury, inflammatory diseases and metabolic disorders. Accumulating evidence indicates that the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome results in the activation of pyroptosis and inflammation. Current evidence suggests that pyroptosis-dependent cell death plays a progressive role in the development of diabetic complications including diabetic wound healing (DWH) and diabetic foot ulcers (DFUs). This review presents a brief overview of the molecular mechanisms underlying pyroptosis and addresses the current research on pyroptosis-dependent signaling pathways in the context of DWH. In this review, we also present some prospective therapeutic compounds/agents that can target pyroptotic signaling pathways, which may serve as new strategies for the effective treatment and management of diabetic wounds.

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Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats

Cited by 9 publications

References 47 publications

16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer

16S rRNA seq-identified Corynebacterium promotes pyroptosis to aggravate diabetic foot ulcer

Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review

The Mechanism of Pyroptosis and Its Application Prospect in Diabetic Wound Healing

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