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

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.