Transplantation of Cyclic Stretched Fibroblasts Accelerates the Wound-Healing Process in Streptozotocin-Induced Diabetic Mice

Lee, Eunkyung; Kim, Do Yeon; Chung, Eun-Kyung; Lee, Eun Ah; Park, Ki‐Sook; Son, Youngsook

doi:10.3727/096368912x663541

Cited by 35 publications

(46 citation statements)

References 53 publications

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“…A previous study reported that MEBO enhanced α-smooth muscle actin in fibroblasts, indicating that MEBO activates fibroblasts (43). It is hypothesized that leukocytes, including fibroblasts and endothelial cells are the primary origin of VEGF and bFGF (41). Furthermore, bFGF upregulates the expression of VEGF (9,41).…”

Section: Discussionmentioning

confidence: 99%

“…It is hypothesized that leukocytes, including fibroblasts and endothelial cells are the primary origin of VEGF and bFGF (41). Furthermore, bFGF upregulates the expression of VEGF (9,41). Decreased levels of VEGF and/or bFGF, or inhibition of their activity leads to the limited migration of fibroblasts and the delay of wound healing (20,44).…”

Section: Discussionmentioning

confidence: 99%

“…Increases in the number of fibroblasts primarily arise due to the proliferation of resident fibroblasts in response to growth factors, including bFGF, and fibroblasts migrating from the surrounding connective tissue into the wound site (40). It was observed that recombinant bFGF accelerates the wound healing process (14,41), thus, rb-bFGF was used as a positive control for MEBO. In the current study, rb-bFGF promoted the formation of granulation tissue, increased neovascularization and the number of fibroblasts in the granulation tissue, and reduced the time of wound healing, which were all consistent with the effects of MEBO.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…Fibroblasts are proved to be able to improve the wound healing in diabetic animals[16,17]. We hypothesized that PHD2 silenced fibroblasts implantation in diabetic wound would improve wound healing and the progress would be associated with improved neovascularization.…”

Section: Introductionmentioning

confidence: 99%

Wound Healing Improvement with PHD-2 Silenced Fibroblasts in Diabetic Mice

et al. 2013

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BackgroundHypoxia-inducible factor 1α is the central regulator of the hypoxia-induced response which results in the up-regulation of angiogenic factors. Its activity is under precise regulation of prolyl-hydroxylase domain 2. We hypothesized that PHD2 silenced fibroblasts would increase the expression of angiogenic factors, which might contribute to the improvement of the diabetic wound healing. Materials and Methods50 dB/db mice were employed and randomly assigned into five groups with 10 mice in each: group 1 (untreated cell), group 2 (PHD2 silenced cell), group 3 (L-mimosine treated cells), group 4 (nontargeting siRNA treated cells) and group 5 (sham control). Fibroblasts were cultivated from the dermis of mice in each group and treated with PHD2 targeting siRNA, L-mimosine and non-targeting siRNA respectively. A fraction of the fibroblasts were employed to verify the silencing rate of PHD2 after 48 hours. The autologous fibroblasts (treated and untreated) labeled with adenovirus-GFP were implanted around the wound (Φ6mm), which was created on the dorsum of each mouse. The status of wounds was recorded periodically. Ten days postoperatively, 3 mice from each group were sacrificed and wound tissues were harvested. Molecular biological examinations were performed to evaluate the expressions of cytokines. 28 days postoperatively, the remaining mice were sacrificed. Histological examinations were performed to evaluate the densities of GFP+ cells and capillaries. ResultsThe expression of PHD2 reduced to 12.5%, and the expressions of HIF-1α and VEGFa increased significantly after PHD2 siRNA treatment. With the increasing expressions of HIF-1α and VEGFa, the time to wound closure in group 2 was less than 2 weeks. Increased numbers of GFP+ cells and capillaries were observed in group 2. ConclusionPHD2 siRNA treatment not only increased the expression of HIF1α and VEGFa, but also improved the fibroblast proliferation. These effects might contribute to the improvement of the diabetic wound healing.

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“…Despite this, our results add a preliminary contribution to the literature on the effects of tissue stretch on the stiffness of vaginal tissue. Other studies have shown mechanical stretch to be an important factor in extracellular protein synthesis and expression [32], upregulation of collagen [33], growth factor production(10), and changes in tissue compliance [34]. By quantifying tissue stretching with OCE, healing paradigms can be elucidated, which may define appropriate parameters for vaginal tissue mechanotherapy.…”

Section: Discussionmentioning

confidence: 99%

Can We Improve Vaginal Tissue Healing Using Customized Devices: 3D Printing and Biomechanical Changes in Vaginal Tissue

Hakim

Smith²,

Singh

et al. 2018

Gynecol Obstet Invest

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Background: Determining biomechanical changes in vaginal tissue with tissue stretch is critical for understanding the role of mechanotransduction on vaginal tissue healing. Noncontact dynamic optical coherence elastography (OCE) can quantify biomechanical changes in vaginal tissues noninvasively. Improved vaginal tissue healing will reduce postoperative complications from vaginal surgery. Aims: (1) To complete dimensional assessments (DAs) of the vaginal tract. (2) To elucidate biomechanical properties (BMP) of porcine vaginal tissues (PVT). (3) Compare BMPs of piglet and adult PVTs after placement of customized vaginal dilators (VD) by OCE and uniaxial mechanical testing (MT). Methods: Pilot study using adult nulliparous pig and piglet PVTs (n = 20 each). DA of PVTs was performed using silicone molding. 3D-printed VDs were used to achieve different Relative Diameter Change (RDC) of the PVTs (no dilatation, and -50%, 0%, 50% RDC). Elastographic testing using OCE and MT. Results: Using OCE, no significant differences (SD) were noted between adult and piglet PVT (p = 0.74) or by stretch direction (p = 0.300). SD was noted with increasing RDC (p = 0.023). Using MT, there were SD in tissue stiffness between adult and piglet PVT (p = 0.048), but no SD as a function of RDC (p = 0.750) or stretch direction (p = 0.592). Conclusions: This study quantified biomechanical changes in PVT with customized stretching by 3D printed VD using both OCE and MT. This work has implications for the mechanotransduction of vaginal wound healing and noninvasive assessment of vaginal diseases.

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Transplantation of Cyclic Stretched Fibroblasts Accelerates the Wound-Healing Process in Streptozotocin-Induced Diabetic Mice

Cited by 35 publications

References 53 publications

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

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

Wound Healing Improvement with PHD-2 Silenced Fibroblasts in Diabetic Mice

Can We Improve Vaginal Tissue Healing Using Customized Devices: 3D Printing and Biomechanical Changes in Vaginal Tissue

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