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Efficacy of Human Dental-Pulp MSCs Modified by Double-genes on Wound Healing in Diabetic-Foot Model
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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.
result:
The hEDP-MSCs obviously 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 periwound tissue post treatment. Meanwhile, the hEDP-MSCs expressed more CD31 and α-SMA than other groups. Although the hEDP-MSCs expressed more VEGFA and bFGF than hDP-MSCs, they expressed them 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.
other:
no
Bentham Science Publishers Ltd.
Title: Efficacy of Human Dental-Pulp MSCs Modified by Double-genes on Wound Healing in Diabetic-Foot Model
Description:
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.
result:
The hEDP-MSCs obviously 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 periwound tissue post treatment.
Meanwhile, the hEDP-MSCs expressed more CD31 and α-SMA than other groups.
Although the hEDP-MSCs expressed more VEGFA and bFGF than hDP-MSCs, they expressed them 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.
other:
no.
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