Joon Pio Hong

The effect of VEGF on the myogenic differentiation of adipose tissue derived stem cells within thermosensitive hydrogel matrices.

We investigated the combination of human adipose tissue derived stem cells (ADSC) and in vivo gel-forming methoxy poly (ethyleneglycol)-poly (epsilon-caprolactone) (MPEG-PCL) as a muscle regeneration matrix, with and without inclusion of vascular endothelial cell growth factor (VEGF). VEGF(165)-treated stem cell grafts showed significant proliferation and differentiation into muscle tissue in vivo. Importantly, the inclusion of VEGF enhanced vascularization. This scaffold supported preconditioned ADSC, and allowed them to differentiate into mature muscle tissues in vivo, indicating that ADSC of human origin and MPEG-PCL scaffolds provided an appropriate environment for cellular growth and expansion. Our results thus provide a potential solution to the major obstacle encountered in the engineering of thick complex tissues, which require an adequate blood supply to maintain cell viability during tissue growth and to induce appropriate structural organization. Therefore, the combination of ADSC and in vivo gel-forming MPEG-PCL with VEGF(165) might serve as a suitable non-invasive biomaterial for clinical muscle regeneration applications.

Recombinant Human Epidermal Growth Factor Accelerates Recovery of Mouse Small Intestinal Mucosa After Radiation Damage

PURPOSE To determine whether systemically administered recombinant human epidermal growth factor (rhEGF) accelerates the recovery of mouse small intestinal mucosa after irradiation. METHODS AND MATERIALS A mouse mucosal damage model was established by administering radiation to male BALB/c mice with a single dose of 15 Gy applied to the abdomen. After irradiation, rhEGF was administered subcutaneously at various doses (0.04, 0.2, 1.0, and 5.0 mg/kg/day) eight times at 2- to 3-day intervals. The evaluation methods included histologic changes of small intestinal mucosa, change in body weight, frequency of diarrhea, and survival rate. RESULTS The recovery of small intestinal mucosa after irradiation was significantly improved in the mice treated with a high dose of rhEGF. In the mice that underwent irradiation without rhEGF treatment, intestinal mucosal ulceration, mucosal layer damage, and severe inflammation occurred. The regeneration of villi was noticeable in mice treated with more than 0.2 mg/kg rhEGF, and the villi recovered fully in mice given more than 1 mg/kg rhEGF. The frequency of diarrhea persisting for more than 3 days was significantly greater in the radiation control group than in the rhEGF-treated groups. CONCLUSIONS Systemic administration of rhEGF accelerates recovery from mucosal damage induced by irradiation. We suggest that rhEGF treatment shows promise for the reduction of small intestinal damage after irradiation.

Epidermal growth factor competes with EGF receptor inhibitors to induce cell death in EGFR-overexpressing tumor cells.

Epidermal growth factor receptor (EGFR) signaling plays an important role in cell growth and differentiation. Mutations in the EGFR gene and EGFR gene amplifications have been associated with increased responsiveness to selective EGFR tyrosine kinase inhibitors (EGFR-TKIs). By contrast, EGF may also stimulate apoptosis in tumor cells, depending on EGFR and Her2 (erbB-2) expression levels. In the present study, we investigated cellular responses after EGFR activation by EGF, or inhibition by cetuximab and gefitinib. EGF treatment induced a near-immediate increase in p38 MAPK phosphorylation together with inactivation of ERK1/2. In contrast, gefitinib- and cetuximab-induced phosphorylation of p38 MAPK was much delayed, and gefitinib also induced a delayed activation of ERK1/2. EGF induced progressive cell death of A431 cells with prolonged treatment, whereas cetuximab- or gefitinib-treated cells showed temporary growth arrest and subsequent re-growth. Moreover, in combination treatment experiments, cetuximab or gefitinib competitively inhibited EGF-induced cell death. Normal WI38-VA13 cells did not display any noticeable changes in cell proliferation in response to EGF, gefitinib or cetuximab. EGF-induced death signaling is apparently irreversible: EGF induced significant EGFR phosphorylation/internalization and activated caspase-3, -8 and -9, effects that were not observed in cetuximab- or gefitinib-treated cells. Collectively, these results indicate that EGF may be a more potent cytotoxic agent than EGFR blockers in EGFR-overexpressing cancer cells.

The effect of various concentrations of human recombinant epidermal growth factor on split‐thickness skin wounds

Epidermal growth factor (EGF) is a potent stimulant of epithelialisation. However, topical application of EGF to achieve facilitated re‐epithelialisation in partial thickness wounds has been controversial. A total of 10 pigs, each with eight 4 × 4 cm partial thickness wounds, were treated twice a day for 10 days to observe the effect of human recombinant EGF in concentrations of 0·1, 1, 5, 10, 25 ug/g, vehicle only and two controls. The control and the vehicle‐only wounds each demonstrated 100% healing time (HT100) of 9·31 ± 1·34 and 8·5 ± 1·12 while the wounds treated with EGF ointment with concentrations of 0·1 (HT100 = 6·4 ± 0·71), 1 (HT100 = 5·2 ± 0·63), 5 (HT100 = 5·8 ± 0·85), 10 (HT100 = 7·1 ± 1·45) and 25 ug/g (HT100 = 7·4 ± 0·57) demonstrated significant reduction in time to achieve re‐epithelialisation. Among the EGF‐treated wounds, the wounds treated with EGF concentrations of 1 and 5 ug/g achieved the fastest re‐epithelialisation with evidence of substantial increase in basal keratinocyte activity observed through Ki‐67 activity. In conclusion, this article demonstrates the efficacy of human recombinant EGF in facilitating re‐epithelialisation of partial thickness wounds with the most efficient healing found in EGF concentrations of 1 and 5 ug/g.

The combined effect of recombinant human epidermal growth factor and erythropoietin on full‐thickness wound healing in diabetic rat model

Diabetic wound is a chronic wound in which normal process of wound healing is interrupted. Lack of blood supply, infection and lack of functional growth factors are assumed as some of the conditions that lead to non‐healing environment. Epidermal growth factor (EGF) acts primarily to stimulate epithelial cell growth across wound. Erythropoietin (EPO) is a haematopoietic factor, which stimulates the production, differentiation and maturation of erythroid precursor cells. This study hypothesised combining these two factors, non‐healing process of diabetic wound will be compensated and eventually lead to acceleration of wound healing compared with single growth factor treatment. A total of 30 diabetic Sprague–Dawley rats were divided into three treatment groups (single treatment of rh‐EPO or rh‐EGF or combined treatment on a full‐thickness skin wound). To assess the wound healing effects of the components, the wound size and the healing time were measured in each treatment groups. The skin histology was examined by light microscopy and immunohistochemical analysis of proliferating markers was performed. The combined treatment with rh‐EPO and rh‐EGF improved full‐thickness wound significantly (P < 0·05) accelerating 50% healing time with higher expression of Ki‐67 compared with single growth factor‐treated groups. The combined treatment failed to accelerate the total healing time when compared with single growth factor treatments. However, the significant improvement were found in wound size reduction in the combined treatment group on day 4 against single growth factor‐treated groups (P < 0·05). This study demonstrated that the combined treatment of rh‐EPO and rh‐EGF improved the wound healing possibly through a synergistic action of each growth factor. This application provides further insight into combined growth factor therapy on non‐healing diabetic wounds.

An Algorithm for Limb Salvage for Diabetic Foot Ulcers

The treatment of diabetic foot ulceration is complex with multiple considerations often leading to limb amputation. This article presents the usefulness of a multidisciplinary approach along with an algorithm to manage and salvage diabetic foot ulcers from amputation. This algorithm is a step-by-step guide to manage the diabetic foot ulcer and can help one in the selection of patients for limb salvage reconstruction.

The use of recombinant human epidermal growth factor to promote healing for chronic radiation ulcer.

This case report describes the first successful use of recombinant human epidermal growth factor (rh‐EGF) in radiation‐induced chronic wound of bone and skin which remains to be difficult to treat. Such wound on the chest of a 59‐year‐old female patient is presented lasting 3 years despite flap surgery and conventional treatment. The treatment with rh‐EGF achieved healing within 16 weeks but further study to evaluate its potential for radiation‐induced chronic wounds is warranted.

Epidermal growth factor induces cell death in the absence of overexpressed epidermal growth factor receptor and ErbB2 in various human cancer cell lines.

ABSTRACT Epidermal growth factor (EGF) stimulates apoptosis in tumor cells depending on the expression levels of EGF receptor and Her2. We examined the protein levels in 22 different cancer cell lines and assessed the responses to EGF. EGF-induced cytotoxicity was not correlated with the levels of either EGFR or Her2. Fourteen cell lines exhibited decreased cell proliferation, whereas 293T cells did not display any noticeable changes and degraded transiently expressed EGFR following EGF treatment. EGF treatment resulted in significant tumor growth inhibition in some xenografts. Our data indicate that exogenous EGF treatment leads to growth inhibition rather than inducing tumor cell proliferation.

Reconstruction of lower extremity with perforator free flaps by free style approach in pediatric patients.

Pediatric reconstruction using microsurgery is accepted normal practice, and the use of perforator flaps is slowly increasing. This study presents clinical work using various perforator free flaps by free style approach to reconstruct lower extremity soft tissue defects in pediatric patients and evaluates its efficacy. Between June 2002 and February 2011, 32 cases (mean age: 10.1 years) were reconstructed with free style perforator free flaps. Retrospective evaluations for flap survival, growth character, and other associated morbidities were performed. Flaps used in this series are anterolateral thigh (ALT) perforator, superficial circumflex iliac artery perforator (SCIP), upper medial thigh perforator, and posterior interosseous perforator free flaps. The free style approach for pedicle dissection was successful in all cases. Early postoperative complications were 15.6% from hematoma collection to partial loss of flap. Although there was no total loss in this series, one case needed additional flap coverage to cover the partial loss of the flap. The long-term follow-up showed contracture along the margin, with 16% needing a releasing procedure. Bone growth was not affected by flap contracture. The overall results show perforator flaps using the free style approach to be a reliable and feasible approach for lower extremity reconstruction in the pediatric population.

Three-wall orbital decompression in Graves ophthalmopathy for improvement of vision.

Graves ophthalmopathy can result in progressive visual loss. Four patients with deteriorating vision despite steroid therapy and/or radiotherapy underwent three-wall orbital decompression through an extended subciliary incision for the preservation of vision. The authors evaluated the visual outcome and morbidity after three-wall orbital decompression for patients with Graves ophthalmopathy. Visual acuity improved for all patients without any major complications in the short-term postoperative period (4 weeks), and visual acuity maintained or improved during the follow-up period. The authors conclude that three-wall orbital decompression can be effective in improving the vision of patients with Graves ophthalmopathy whose vision failed to improve with conservative therapy.