Adipose-derived Stromal Cells Overexpressing Vascular Endothelial Growth Factor Accelerate Mouse Excisional Wound Healing

Nauta, Allison; Seidel, Catharina; Deveza, Lorenzo; Montoro, Daniel T.; Grova, Monica; Ko, Sae Hee; Hyun, Jeong S.; Gurtner, Geoffrey C.; Longaker, Michael T.; Yang, Fan

doi:10.1038/mt.2012.234

Cited by 92 publications

(63 citation statements)

References 47 publications

(58 reference statements)

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“…Also, the gene expression profile of the transplanted cells is crucial for their therapeutic effect. [17][18][19] Therefore, next-generation delivery systems should protect bioactive agents in the wound environment, provide sustained release of the bioactive molecules, and adequately modulate the fate, location, and phenotype of transplanted cells.…”

Section: Basic and Experimental Researchmentioning

confidence: 99%

Alginate and DNA Gels Are Suitable Delivery Systems for Diabetic Wound Healing

Tellechea

Silva

Min

et al. 2015

The International Journal of Lower Extremity Wounds

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Diabetic foot ulcers (DFU) represent a severe health problem and an unmet clinical challenge. In this study, we tested the efficacy of novel biomaterials in improving wound healing in mouse models of diabetes mellitus (DM). The biomaterials are composed of alginate-and deoxyribonucleic acid (DNA)-based gels that allow incorporation of effector cells, such as outgrowth endothelial cells (OEC), and provide sustained release of bioactive factors, such as neuropeptides and growth factors, which have been previously validated in experimental models of DM wound healing or hind limb ischemia. We tested these biomaterials in mice and demonstrate that they are biocompatible and can be injected into the wound margins without major adverse effects. In addition, we show that the combination of OEC and the neuropeptide Substance P has a better healing outcome than the delivery of OEC alone, while subtherapeutic doses of vascular endothelial growth factor (VEGF) are required for the transplanted cells to exert their beneficial effects in wound healing. In summary, alginate and DNA scaffolds could serve as potential delivery systems for the next-generation DFU therapies.

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Section: Basic and Experimental Researchmentioning

confidence: 99%

Alginate and DNA Gels Are Suitable Delivery Systems for Diabetic Wound Healing

Tellechea

Silva

Min

et al. 2015

The International Journal of Lower Extremity Wounds

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“…VEGF and bFGF, however, are decreased in delayed cutaneous wounds, including diabetic wounds and chronic ulcers (17)(18)(19). Inhibition of VEGF and bFGF by neutralizing antibodies results in a decrease in the migration of fibroblasts and a delay in wound healing (20), while treatment with recombinant bFGF and VEGF, or overexpression of VEGF accelerates wound healing (14,21,22). Therefore, it is a potentially clinically beneficial to increase the levels of VEGF and bFGF in cutaneous wounds, particularly in delayed wound healing.…”

Section: Introductionmentioning

confidence: 99%

Moist exposed burn ointment promotes cutaneous excisional wound healing in rats involving VEGF and bFGF

Tang

Han

Feng

et al. 2014

Molecular Medicine Reports

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Abstract. Cutaneous delayed wounds are a challenging clinical problem, and vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) exhibit key roles in wound healing. Moist exposed burn ointment (MEBO), a Chinese burn ointment with a USA patented formulation, has been reported to promote chronic ischemic and neurogenic ulcer healing in patients; however, the underlying mechanisms remain unclear. In the present study, MEBO significantly promoted the formation of granulation tissue in cutaneous excisional wounds, shortened the time of wound healing, and increased neovascularization and the number of fibroblasts. Furthermore, as well as enhancing the protein expression, MEBO application also increased the gene expression of VEGF and bFGF. The results indicate that MEBO promotes cutaneous excisional wound healing by at least partially enhancing VEGF and bFGF production, implicating the potential uses of MEBO for delayed cutaneous wound healing. IntroductionCutaneous wounds, known as ulcers, are an extremely common clinical problem and often arise following acute or chronic mechanical causes, physical or chemical burns, frostbite, infections, and disorders, including rheumatism, diabetes, peripheral vascular disease, lipodermatosclerosis and malignant tumors (1,2). Furthermore, cutaneous wound healing may be significantly delayed due to the aforementioned factors. At present, delayed cutaneous wounds are one of major burdens for health care, and lead to a reduced quality of life in patients who suffer from this type of wound (3,4).Wound healing is a complicated biological process involving a series of dynamic events, including hemostasia, inflammation, cell proliferation and differentiation, neovascularization, granulation tissue formation, collagen synthesis, epithelialization, and wound contraction. Increasing evidence has established the hypothesis that growth factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are key regulators of normal and abnormal angiogenesis, and tissue repair in animals and humans (5-8). VEGF promotes angiogenesis/vasculogenesis and vascular permeability, and enhances endothelial cell proliferation and migration as well as the adhesion of leukocytes (5,9). Further research revealed that VEGF stimulates hydrogen sulfide synthesis and release from endothelial cells, thus leading to subsequent endothelial cell growth, migration and permeability, microvessel formation, and wound healing (10). In addition, VEGF promotes epithelialization and collagen deposition in the wound (11). FGF-2, known as bFGF, is a member of a large FGF family and induces angiogenesis, endothelial cell and fibroblast proliferation, and wound healing (12)(13)(14). Recent data indicated that bFGF-mediated angiogenesis refers to endothelial cell proliferation, migration and tube formation by activating c-Jun N-terminal kinase/stress-activated protein kinase signaling (15). Notably, the expression of VEGF and bFGF was increased following skin in...

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“…[53][54][55] MSCs are multipotent cells that can differentiate along different tissue-specific pathways, including bone cells (osteoblasts), cartilage cells (chondrocytes), and fat cells (adipocytes). 56 Most of these differentiations require directed induction. For example, our previous study demonstrated that without induction for chondrogenic differentiation, MSCs would not differentiate until 4 weeks.…”

Section: Discussionmentioning

confidence: 99%

<I>β</I>-Cyclodextrin-Linked Polyethylenimine Nanoparticles Facilitate Gene Transfer and Enhance the Angiogenic Capacity of Mesenchymal Stem Cells for Wound Repair and Regeneration

Peng¹,

Wei²,

Shan³

et al. 2015

j biomed nanotechnol

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Repair of deep wounds by cell transplantation strongly depends on angiogenesis and on the regeneration of skin and appendages. In this study, plasmid DNA encoding vascular endothelial growth factor-165 (VEGF-165) was transduced into bone-marrow mesenchymal stem cells (MSCs) using a nonviral vector, -cyclodextrin-linked polyethylenimine, to enhance angiogenic capacity. The effects of MSCs administered by intradermal injection or transplantation on wound closure were compared in a full-thickness excision wound model. The results showed that the MSC-seeded sponge had significantly stronger acceleration in wound closure than the MSC injection. The effects on wound repair and regeneration of transplanted MSCs and pDNA-VEGF165-transfected MSCs (TMSCs) with gelatin/ -tricalcium phosphate scaffold were also investigated. Compared with MSC transplantation, TMSC transplantation showed higher efficacy in stimulating wound closure, promoting dermal collagen synthesis and regulating the deposition of newly formed collagen. In addition, the angiogenic capacity of the TMSCs was higher than that of the MSCs. The results indicate that the nonviral genetic engineering of the MSCs is a promising strategy to enhance the angiogenic capacity of MSCs for wound repair and angiogenesis. Functional gene-activated MSCs may be used as cost-effective and accessible seed cells for skin tissue engineering and as novel carriers for wound gene therapy.

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Adipose-derived Stromal Cells Overexpressing Vascular Endothelial Growth Factor Accelerate Mouse Excisional Wound Healing

Cited by 92 publications

References 47 publications

Alginate and DNA Gels Are Suitable Delivery Systems for Diabetic Wound Healing

Alginate and DNA Gels Are Suitable Delivery Systems for Diabetic Wound Healing

Moist exposed burn ointment promotes cutaneous excisional wound healing in rats involving VEGF and bFGF

<I>β</I>-Cyclodextrin-Linked Polyethylenimine Nanoparticles Facilitate Gene Transfer and Enhance the Angiogenic Capacity of Mesenchymal Stem Cells for Wound Repair and Regeneration

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