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The effects of insulin-like growth factor-1 gene therapy and cell transplantation on rat acute wound model
Fereshteh Talebpour Amiri1, Fatemeh Fadaei Fathabadi1, Mahnaz Mahmoudi Rad2
1Department of Anatomy, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, IR Iran.
Background:
Wound healing is a complex process. Different types of skin cells, extracellular matrix and variety of growth factors are involved in wound healing. The use of recombinant growth factors in researches and production of skin substitutes are still a challenge.
Objectives:
Much research has been done on the effects of gene therapy and cell therapy on wound healing. In this experimental study, the effect of insulin-like growth factor (IGF-1) gene transfer in fibroblast cells was assessed on acute dermal wound healing.
Materials And Methods:
Fibroblasts were cultured and transfected with IGF-1. Lipofectamine 2000 was used as a reagent of transfection. Transgene expression levels were measured by the enzyme linked immunosorbent assay (ELISA). To study in vivo, rats (weighing 170-200 g) were randomly divided into three groups (five/group) and full-thickness wounds were created on the dorsum region. Suspensions of transfected fibroblast cells were injected into the wound and were compared with wounds treated with native fibroblast cells and normal saline. For the microscopic examination, biopsy was performed on day seven.
Results:
In vitro, the maximum expression of IGF1 (96.95 pg/mL) in transfected fibroblast cells was 24 hours after gene transfer. In vivo, it was clear that IGF-1 gene therapy caused an increase in the number of keratinocyte cells during the wound healing process (mean of group A vs. group B with P value = 0.01, mean of group A vs. group C with P value = 0.000). Granulation of tissue formation in the transfected fibroblast group was more organized when compared with the normal saline group and native fibroblast cells.
Conclusions:
This study indicated that the optimization of gene transfer increases the expression of IGF-1. High concentrations of IGF-1, in combination with cell therapy, have a significant effect on wound healing.
Insights
Gene therapy using insulin-like growth factor-1 (IGF-1) in fibroblasts significantly enhances acute dermal wound healing. This approach optimizes IGF-1 expression, promoting keratinocyte proliferation and organized tissue formation for improved healing outcomes.
Area of Science:
- Regenerative Medicine
- Molecular Biology
- Dermatology
Background:
- Wound healing is a complex biological process involving cells, extracellular matrix, and growth factors.
- Recombinant growth factor application and skin substitute production present research challenges.
- Gene and cell therapies are being explored for their potential to improve wound healing.
Purpose of the Study:
- To investigate the effect of insulin-like growth factor-1 (IGF-1) gene transfer into fibroblast cells on acute dermal wound healing.
- To assess the efficacy of IGF-1 gene-modified fibroblasts in promoting wound repair.
Main Methods:
- Fibroblast cells were cultured and transfected with the IGF-1 gene using Lipofectamine 2000.
- Transgene expression was quantified using enzyme-linked immunosorbent assay (ELISA).
- In vivo study involved creating full-thickness wounds in rats, treated with transfected fibroblasts, native fibroblasts, or normal saline, followed by microscopic examination.
Main Results:
- In vitro, peak IGF-1 expression in transfected fibroblasts occurred 24 hours post-transfection.
- In vivo, IGF-1 gene therapy significantly increased keratinocyte cell numbers in healing wounds (P < 0.01).
- Transfected fibroblast treatment resulted in more organized granulation tissue formation compared to controls.
Conclusions:
- Optimized gene transfer effectively increases IGF-1 expression.
- High concentrations of IGF-1, when combined with cell therapy, demonstrate a significant positive impact on wound healing.
- IGF-1 gene-modified fibroblasts show promise for enhancing dermal wound repair.
