Heat shock-pretreated bone marrow mesenchymal stem cells accelerate wound healing in a diabetic foot ulcer rat model

IF 3.2 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Diabetic Medicine Pub Date : 2025-02-09 DOI:10.1111/dme.15507

Xi Lin, Qi Lin

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引用次数: 0

Abstract

Background

Diabetic foot ulcers (DFUs) are the severe chronic complications of diabetes, amputation is required when ulcers cause severe loss of tissue or evoke a life-threatening infection. Mesenchymal stem cells (MSCs) have shown a good effect in helping DFU healing, though the efficiency needs to be improved. This study aimed to investigate the effects of heat shock pretreatment on the improvement of the therapeutic effects of MSCs.

Methods

Primary rat bone marrow MSCs (BMSCs) were isolated and stimulated with heat shock pretreatment and then tested on a DFU rat model. Alkaline phosphatase, Alizarin Red S, and Oil Red O were stained to check the osteogenic differentiation ability of heat shock-pretreated BMSCs. The effect of heat shock pretreatment on the inflammatory response of macrophages was studied with the lipopolysaccharides stimulation model on a mouse macrophage cell line RAW264.7. The impact of heat shock-pretreated BMSCs on dermal fibroblasts was also checked. Last, heat shock-pretreated BMSCs were tested on a DFU rat model.

Results

Heat shock-pretreated BMSCs were characterized by the expression of CD105 and CD44. Heat shock pre-stimulation did not affect cell viability when cultured up to 96 h. Heat shock pre-stimulated BMSCs inhibited the inflammatory response by reducing the pro-inflammatory cytokine production (IL-1β, IL-6, and TNF-α) and enhancing the anti-inflammatory cytokine production (IL-10) (at least all p < 0.01), as well as increasing the ratio of M2 polarization macrophages to M1 polarization in vitro (p < 0.001). Heat shock pre-stimulated BMSCs enhanced the growth and migration of dermal fibroblasts in vitro (p < 0.001). Heat shock-BMSCs promoted the M2 polarization level of macrophages in wound tissues in a DFU rat model.

Conclusion

Heat shock pretreatment could enhance the therapeutic effect of BMSCs on wound healing in a DFU rat model.

查看原文本刊更多论文

热休克预处理骨髓间充质干细胞促进糖尿病足溃疡大鼠模型伤口愈合。

背景：糖尿病足溃疡（DFUs）是糖尿病的严重慢性并发症，当溃疡引起严重的组织损失或引起危及生命的感染时，需要截肢。间充质干细胞（Mesenchymal stem cells, MSCs）在帮助DFU愈合方面已显示出良好的效果，但其效率有待提高。本研究旨在探讨热休克预处理对MSCs治疗效果的改善作用。方法：分离大鼠原代骨髓间充质干细胞（BMSCs），经热休克预处理后进行DFU大鼠模型检测。采用碱性磷酸酶、茜素红S、油红O染色检测热休克预处理的骨髓间充质干细胞成骨分化能力。采用脂多糖刺激小鼠巨噬细胞RAW264.7模型，研究热休克预处理对巨噬细胞炎症反应的影响。热休克预处理的骨髓间充质干细胞对真皮成纤维细胞的影响也被检测。最后，热休克预处理的骨髓间充质干细胞在DFU大鼠模型上进行检测。结果：热休克预处理的骨髓间充质干细胞具有CD105和CD44的表达特征。热休克预刺激在培养96 h后不影响细胞活力。热休克预刺激的骨髓间充质干细胞通过减少促炎细胞因子（IL-1β、IL-6和TNF-α）的产生和增强抗炎细胞因子（IL-10）的产生来抑制炎症反应（至少全部p）。结论：热休克预处理可增强骨髓间充质干细胞对DFU大鼠模型创面愈合的治疗作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetic Medicine 医学-内分泌学与代谢

CiteScore

7.20

自引率

5.70%

发文量

229

审稿时长

3-6 weeks

期刊介绍： Diabetic Medicine, the official journal of Diabetes UK, is published monthly simultaneously, in print and online editions. The journal publishes a range of key information on all clinical aspects of diabetes mellitus, ranging from human genetic studies through clinical physiology and trials to diabetes epidemiology. We do not publish original animal or cell culture studies unless they are part of a study of clinical diabetes involving humans. Categories of publication include research articles, reviews, editorials, commentaries, and correspondence. All material is peer-reviewed. We aim to disseminate knowledge about diabetes research with the goal of improving the management of people with diabetes. The journal therefore seeks to provide a forum for the exchange of ideas between clinicians and researchers worldwide. Topics covered are of importance to all healthcare professionals working with people with diabetes, whether in primary care or specialist services. Surplus generated from the sale of Diabetic Medicine is used by Diabetes UK to know diabetes better and fight diabetes more effectively on behalf of all people affected by and at risk of diabetes as well as their families and carers.”