Efficacy of Human Dental-Pulp MSCs Modified by Double-genes on Wound Healing in Diabetic-Foot Model.

Current stem cell research & therapy Pub Date : 2025-02-28 DOI:10.2174/011574888X363143250221015057

Guangchang Zhu, Hongfang Meng, Yuefeng Yang, Qian Yuwen, Yong Zhou, Menghu Han, Xia Xia, Shiwei Song

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Abstract

Objectives: Diabetic foot (DF) poses a great challenge to us due to its poor therapeutic effect. To seek a new cure, the human dental pulp mesenchymal stem cells (hDP-MSCs) were modified by vascular endothelial growth factor A (VEGFA) and basic fibroblast growth factor (bFGF) (hEDP-MSCs) to investigate their curative effect on DF wound in animal models.

Methods: Forty-eight rats with DF constructed with streptozotocin and ligation of femoral arteries, were randomly divided into six equal groups, which respectively received an intramuscular injection of normal saline (Control group), hDP-MSCs, VEGFA-modified hDP-MSCs, bFGF-- modified hDP-MSCs, hEDP-MSCs, and Ad.VEGF.FGF (Ad.FV). The tissues around DF wound were collected to investigate the level of CD31, alpha-smooth muscle actin (α-SMA), and cytokines. The expression of Notch1, Hes1, and CD105 were assessed via Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) after administration.

Results: The hEDP-MSCs increased capillaries and decreased wound area (%). QRT-PCR showed that hEDP-MSCs over-expressed the mRNA of Notch1, hairy and enhancer of split 1 and CD105 in peri-wound tissue post-treatment. Meanwhile, the hEDP-MSCs expressed more CD31 and α-SMA than other groups. The hEDP-MSCs expressed more VEGFA and bFGF than hDP-MSCs, and yet less than Ad.FV. Compared with hDP-MSCs, the hEDP-MSCs down-regulated the expressions of interleukin-1 beta (IL-1β), interleukin (IL-6), and tissue necrosis factor α (TNF-a) post-treatment.

Conclusion: This study highlights the curative effect of hEDP-MSCs in the wound healing process, and demonstrates the decisive function of hEDP-MSCs in promoting angiogenesis and reducing inflammation.

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双基因修饰人牙髓间充质干细胞对糖尿病足模型创面愈合的影响。

目的：糖尿病足（DF）的治疗效果不佳，给我们带来了很大的挑战。为寻求治疗牙髓间充质干细胞的新途径，采用血管内皮生长因子a （VEGFA）和碱性成纤维细胞生长因子（bFGF）对人牙髓间充质干细胞（hDP-MSCs）进行修饰，在动物模型上研究其对DF创面的治疗效果。方法：采用链脲佐菌素和股动脉结扎构建DF的大鼠48只，随机分为6组，分别肌内注射生理盐水（对照组）、hDP-MSCs、vegf -修饰hDP-MSCs、bFGF-修饰hDP-MSCs、hEDP-MSCs和Ad.VEGF.FGF （Ad.FV）。收集DF创面周围组织，观察CD31、α-平滑肌肌动蛋白（α-SMA）和细胞因子水平。给药后通过实时荧光定量聚合酶链反应（qRT-PCR）检测Notch1、Hes1和CD105的表达。结果：hEDP-MSCs增加了毛细血管，减少了伤口面积（%）。QRT-PCR结果显示hEDP-MSCs处理后创面周围组织中Notch1、hairy、split 1增强子和CD105 mRNA过表达。hEDP-MSCs表达的CD31和α-SMA均高于其他各组。hEDP-MSCs比hDP-MSCs表达更多的VEGFA和bFGF，但低于Ad.FV。与hDP-MSCs相比，hDP-MSCs治疗后下调白细胞介素-1β (IL-1β)、白细胞介素（IL-6）和组织坏死因子α (TNF-a)的表达。结论：本研究突出了hEDP-MSCs在创面愈合过程中的疗效，证明了hEDP-MSCs在促进血管生成和减轻炎症方面的决定性作用。

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Current stem cell research & therapy

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