Mesenchymal stem cell therapy for non-healing diabetic foot ulcer infection: New insight

Mahmoudvand, Golnaz; Rouzbahani, Arian Karimi; Razavi, Zahra; Mahjoor, Mohamad; Afkhami, Hamed

doi:10.3389/fbioe.2023.1158484

Cited by 22 publications

(13 citation statements)

References 94 publications

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“… 40 Increased expression of c‐JUN is associated with reduced production of matrix metalloproteinases, promoting wound healing in diabetic mice. 41 Hyperglycaemia mediates increased JUND expression, promoting the production of pro‐inflammatory cytokines. 42 In diabetic wounds, TNFAIP3 has been found to be involved in the production of IL‐1β.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential immunologic resilience in the healing process of diabetic foot ulcers

Cheng,

Ren,

Niyazi

et al. 2023

International Wound Journal

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Diabetic foot ulcers (DFUs) are one of the most common and challenging complications of diabetes, yet our understanding of their pathogenesis remains limited. We collected gene expression data of DFU patients from public databases. Bioinformatics tools were applied for systematic analysis, including the identification of differentially expressed genes (DEGs), weighted gene co‐expression network analysis (WGCNA) and enrichment analysis. We further used single‐cell RNA sequencing to identify the distribution of different cell populations in DFU. Finally, key results were validated using reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and flow cytometry. We identified 217 DEGs between ulcerated and healthy skin, and 37 DEGs between healing ulcers and ulcers. WGCNA revealed that the cyan module had the highest positive correlation with healthy skin and negative correlation with ulcers. The black module had the highest negative correlation with healthy skin and positive correlation with ulcers. Enrichment analysis showed that the genes in the cyan module were mainly associated with complement and coagulation cascades, while the genes in the black module were mainly associated with the IL‐17 signalling pathway. In addition, CD8 T cells were significantly lower in ulcers than in healthy and healing ulcers. By comparing marker genes of CD8 T cells, we identified key genes in the cyan and black modules and validated their expression using RT‐qPCR. The proportion of CD8 T cells was increased in healing ulcers. Flow cytometry detected increased levels of CD8 T, B and natural killer cells in healing ulcers. CD8 T cells and related key genes play an important role in the healing process of DFU. The results of this study provide a new perspective for understanding the pathogenesis and treatment of DFU.

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Section: Discussionmentioning

confidence: 99%

Identification of potential immunologic resilience in the healing process of diabetic foot ulcers

Cheng,

Ren,

Niyazi

et al. 2023

International Wound Journal

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“…As previously stated, the healing process of skin wounds is intricate and involves various phases, namely homeostasis, inflammation, proliferation, and remodeling. MSCs are known to participate in all phases of the wound-healing process, thereby exerting therapeutic benefits ( Mahmoudvand et al, 2023 ).…”

Section: Mscs and Healing Of Anaerobic Bacterial Wound Infection In H...mentioning

confidence: 99%

“…MSCs have the potential to transform into skin substitutes, thereby acting as a viable alternative to dermal fibroblasts in the process of epidermis generation and skin wound healing. They are capable of differentiating into several cell types in injured areas, including dermal fibroblasts, keratinocytes, and endothelial cells ( Hermann et al, 2023 ; Mahmoudvand et al, 2023 ; Nilforoushzadeh et al, 2023 ). Apart from their differential ability, MSCs have additional characteristics, such as being easily harvested and showing minimal immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

Application of hypoxia-mesenchymal stem cells in treatment of anaerobic bacterial wound infection: wound healing and infection recovery

Andalib,

Kashfi,

Mahmoudvand

et al. 2023

Front. Microbiol.

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Mesenchymal stromal cells, commonly referred to as MSCs, are a type of multipotent stem cells that are typically extracted from adipose tissue and bone marrow. In the field of tissue engineering and regenerative medicine, MSCs and their exosomes have emerged as revolutionary tools. Researchers are now devoting greater attention to MSCs because of their ability to generate skin cells like fibroblasts and keratinocytes, as well as their distinctive potential to decrease inflammation and emit pro-angiogenic molecules at the site of wounds. More recent investigations revealed that MSCs can exert numerous direct and indirect antimicrobial effects that are immunologically mediated. Collectively, these antimicrobial properties can remove bacterial infections when the MSCs are delivered in a therapeutic setting. Regardless of the positive therapeutic potential of MSCs for a multitude of conditions, transplanted MSC cell retention continues to be a major challenge. Since MSCs are typically administered into naturally hypoxic tissues, understanding the impact of hypoxia on the functioning of MSCs is crucial. Hypoxia has been postulated to be among the factors determining the differentiation of MSCs, resulting in the production of inflammatory cytokines throughout the process of tissue regeneration and wound repair. This has opened new horizons in developing MSC-based systems as a potent therapeutic tool in oxygen-deprived regions, including anaerobic wound infection sites. This review sheds light on the role of hypoxia-MSCs in the treatment of anaerobic bacterial wound infection in terms of both their regenerative and antimicrobial activities.

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“…9,10 Although PRP and stem cells act similarly in DFU treatment, their efficacies and underlying mechanisms are possibly different. Publications exploring the therapeutic effects of each method are often found in literature review, 11,12 and those comparing the therapeutic effects of the two treatments, however, have been rarely reported. The present study was designed to compare the efficacy of PRP gel and UC-MSCs gel in the treatment of DFU, providing more evidence-based medical evidence for the two treatments.…”

Section: Introductionmentioning

confidence: 99%

Comparative study on the efficacy of PRP gel and UC‐MSCs gel as adjuvant therapies in the treatment of DFU wounds

Jin,

Meng,

Zhang

et al. 2024

Skin Research and Technology

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BackgroundDiabetic foot ulcer (DFU) is a common and serious complication of diabetes, and its treatment is challenging. Platelet‐rich plasma (PRP) gel and umbilical cord mesenchymal stem cells (UC‐MSCs) gel have been concerned as new therapies for DFU in recent years, and comparative studies on the efficacy and mechanisms of these methods, however, are rarely reported.MethodsThirty patients with DFU were selected and divided into the PRP group and the UC‐MSCs group, and wound healing, foot blood vessels (ABI index), infection index (CRP), neuropathy symptoms (TCSS score), and foot skin temperature before and after treatment were compared between the two groups. SPSS 21.0 was used for statistical analysis.ResultsThe results showed that the efficacy of the UC‐MSCs gel group was significantly better than that of the PRP group in terms of wound healing rate, time to complete wound closure, ABI index, CRP level and TCSS score. No statistically significant difference in foot skin temperature was observed between the two groups.ConclusionThe efficacy of UC‐MSCs gel is significantly superior to that of PRP gel in the treatment of DFU, with shortened time to complete wound closure, increased wound healing rate, better pain and infection control, and improved vascular and neurological symptoms.

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Mesenchymal stem cell therapy for non-healing diabetic foot ulcer infection: New insight

Cited by 22 publications

References 94 publications

Identification of potential immunologic resilience in the healing process of diabetic foot ulcers

Identification of potential immunologic resilience in the healing process of diabetic foot ulcers

Application of hypoxia-mesenchymal stem cells in treatment of anaerobic bacterial wound infection: wound healing and infection recovery

Comparative study on the efficacy of PRP gel and UC‐MSCs gel as adjuvant therapies in the treatment of DFU wounds

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