Correction of Primary Multiple Upper Eyelid Folds by Three Mini-Incision Upper Blepharoplasty and Simultaneous Orbital Fat Pad Repositioning in East Asians.

BACKGROUND: This study aims to assess the feasibility and efficacy of a three mini-incision upper blepharoplasty combined with simultaneous orbital fat pad repositioning for correcting primary multiple upper eyelid folds in East Asians. METHODS: A retrospective analysis of 75 patients who underwent three mini-incision double-eyelid blepharoplasty in conjunction with orbital fat pad repositioning for the correction of multiple upper eyelid folds between January 2018 and January 2022 was conducted. During the surgery, the lateral extension of the central upper eyelid fat mass was anchored medially to the upper medial eyelid via three small skin incisions. Postoperative follow-up was carried out to evaluate the improvement in multiple upper eyelid folds, and patient satisfaction was measured. RESULTS: The follow-up period ranged from 6 to 36 months, with an average of 12 months. Post-surgery, the multiple fold lines were completely resolved in 71 patients (95%), while relapse occurred in 4 patients (5%). The overall satisfaction rate was 88%. CONCLUSIONS: The three mini-incision double-eyelid blepharoplasty combined with simultaneous orbital fat repositioning is an effective method for correcting primary multiple upper eyelid folds. This technique presents a novel alternative for patients with primary multiple eyelid folds, particularly those who are hesitant to undergo a full-incision double-eyelid procedure. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Surgical Removal of Fat Nodules Formed in the Tear Trough After Autologous Fat Grafting.

BACKGROUND: Autologous fat grafting is a common treatment for tear trough deformities. This procedure involves a potential complication of fat nodule formation, leading to abnormal bulging of the lower eyelid. However, limited information exists about this complication, and an effective treatment is lacking. The present study aimed to present a novel surgical approach for the removal of fat nodules caused by autologous fat grafting in the tear trough. METHODS: This retrospective study included 33 patients who underwent surgery for the removal of fat nodules formed after autologous fat grafting. The procedure was performed using a conjunctival approach, allowing exposure and removal of all fat nodules in the anterior septal space, with the method adapted according to the severity of the deformity. RESULTS: A total of 66 eyelids were treated surgically, including 30 (45.45%) with mild nodular deformity, 23 (34.85%) with moderate nodular deformity, and 13 (10.70%) with severe nodular deformity. A second surgical procedure was required on 3 eyelids (4.56%). The main complications of the surgery were conjunctival congestion (21.21%), and localized depression (18.18%), bruising (12.12%). Among the patients, 29 (87.88%) were satisfied and 4 (12.12%) were dissatisfied with the treatment results. CONCLUSION: Conjunctival approach surgery is an effective method of removing fat nodules formed after autologous fat grafting in the tear trough, with good results and high levels of patient satisfaction. This approach enables the effective management of a common complication of autologous fat grafting and may enable the wider application of autologous fat grafting in the periorbital region. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Use of the Acellular Dermal Matrix (ADM) to Reconstruct Full-thickness Eyelid Defects.

This study aimed to introduce the use of an acellular dermal matrix (ADM) as a posterior lamellar substitution for full-thickness eyelid reconstruction after malignant tumor excision. After resection of the malignant eyelid tumors, anterior lamellar defects were repaired using direct sutures and pedicled flaps in 20 patients (15 men and 5 women). ADM was used to replace the tarsal plate and the conjunctiva. All patients were followed up for 6 months or more to assess the functional and esthetic outcomes of the procedure. The flaps survived in all but 2 cases, wherein they necrosed due to insufficient blood supply. The functionality and esthetic outcomes were excellent in 10 and 9 patients, respectively. There were no changes in visual acuity or corneal epithelial damage after the surgery. The eyeball movement was good. Corneal irritation no longer appeared, and patient comfort was maintained. Furthermore, no tumor recurrence occurred in any patient. ADM is a valuable posterior lamellar material for the full-thickness reconstruction of eyelid defects after the resection of malignant tumors on the eyelids.

Aesthetic Analysis of Alteration of Eyebrow and Forehead Position After Endoscopic Eyebrow lift.

BACKGROUND: Some of the surgeons performing endoscopic brow lift believe that this technique does not lead to clinically significant enlargement of the forehead. PURPOSE: The goal of this study is to determine the change in eyebrow and forehead height after endoscopic brow lift and to assess the durability of the result over time. METHODS: The pre- and postoperative photographs of 97 patients who underwent endoscopic brow lift from January 2016 to July 2020 were standardized and analyzed. The distance between median hairline and upper edge of eyebrow, the distance between upper edge of the eyebrow and edge of the lower eyelid and the distance between edge of the lower eyelid and the nasal base were measured, and the change in the upper face proportion was measured and analyzed. RESULTS: There was statistically significant brow elevation after endoscopic brow lift in all three time periods (less than 1 month, 1-6 months and greater than 6 months). Forehead height did not change to a significant degree, while eyebrow height was increased statistically significant. A longitudinal study on 14 patients for whom multiple follow-up data were available showed that the increase in periorbital height appears to be sustained over time, whereas the change in the forehead height is not as readily apparent, resulting in a bigger relative change in the periorbital compared to the forehead height. CONCLUSIONS: The brow height increased more than the forehead height, corroborating the fact that most of our patients have not complained about forehead becoming larger. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Aesthetic Analysis of Alteration of Eyebrow Position After Double Eyelidplasty.

BACKGROUND: There is an anecdotal belief among some surgeons performing Asian eyelid surgery that double eyelid surgery itself decreases eyebrow position. However, the exact amount of descent and the specific changes in the proportion of facial aesthetics are unknown. PURPOSE: The goal of this study is to determine whether there indeed is a change in brow position after double eyelidplasty and to quantify the proportional differences associated with the change. The three-point double eyelids surgery method was used so that the change in the brow position is solely attributed to the surgery itself and not to the excision of redundant skin. METHODS: From January 2016 to December 2017, double eyelid surgery using the three-point technique was performed on 204 patients who did not require skin excision. Their pre- and postoperative photographs were standardized and analyzed. The ratio of the length between the upper edge of the eyebrow and the edge of the lower eyelid (A) and the length between the edge of the lower eyelid and the nasal base (B) as well as the subsequent change in the midfacial proportion was measured and analyzed. RESULTS: There was a statistically significant brow descent after double eyelidplasty. The average preoperative A/B was 0.71 and the average postoperative A/B was 0.67 (P < 0.001). Although the eyebrow distance did not change in 32.5% of patients, the remaining cohort showed average brow descent of 5.6%. And in this cohort that showed descent, linear regression showed that there was a correlation between the ratio of pre- and postoperative eyebrow distance CONCLUSION: Double eyelid surgery can lower the eyebrow in patients with foldless eyelids. This is in accordance with clinical observation in Asian blepharoplasty. In addition, there are associated changes in the proportion of midfacial aesthetics after the surgery. Such knowledge can be helpful in preoperative consulting with patients as well as in predicting postoperative results. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Effect of Recombinant Human Bone Morphogenetic Protein-2 and Adipose Tissue-Derived Stem Cell on New Bone Formation in High-Speed Distraction Osteogenesis.

PURPOSE: The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) and osteogenically differentiated adipose tissue-derived stem cells (ADSC) on new bone formation in high-speed distraction osteogenesis of adult rabbit cranium were investigated. MATERIALS AND METHODS: A total of 41 adult rabbits were used in the study. Distraction began after a 5-day latency period at a rate of 1.5 mm twice a day until 10-mm length gain was obtained both in the control group, where a bone defect was induced, and in the experimental group, in which ADSC (group A), rhBMP-2 (group B), or both (group C) were injected in the distraction gap after distraction. At 4, 8, and 12 weeks after distraction, computed tomography analysis was done to determine the bone defect dimension and bone mineral density (BMD), while histologic examination was also done to calculate bone formation ratio. RESULTS: Bone defect dimension significantly decreased in groups B and C, compared with the control group, at 4 and 12 weeks after distraction. BMD was significantly increased in groups B and C at 4 weeks. On histologic examination, bone formation ratio was significantly increased in group C only at 12 weeks. CONCLUSION: This study suggests that the use of rhBMP-2 in combination with or without ADSC is helpful to promote bone regeneration in high-speed distraction osteogenesi s of adult rabbit cranium.

MRI molecular imaging using GLUT1 antibody-Fe3O4 nanoparticles in the hemangioma animal model for differentiating infantile hemangioma from vascular malformation.

The purpose of this study is to evaluate the efficacy of glucose transporter protein 1 (GLUT1) antibody-conjugated iron oxide nanoparticles (Fe3O4 NPs) as magnetic resonance imaging (MRI) molecular imaging agents for differentiating infantile hemangioma from vascular malformation in the hemangioma animal model. The conjugation of Fe3O4 NPs with anti-GLUT1 antibodies leads to a significantly increased uptake of NPs by human umbilical vein endothelial cells. MRI imaging following the intravenous injection of GLUT1 antibody-Fe3O4 NPs yielded a significantly lower signal intensity than did unconjugated Fe3O4 NPs. Upon histological examination of the GLUT1 antibody-Fe3O4 NPs, Prussian blue-stained NPs were identified in CD31-positive endothelial cells of hemangioma. In contrast, when treated with unconjugated Fe3O4 NPs, Prussian blue-stained NPs were found in macrophages rather than in endothelial cells. GLUT1 antibody conjugation can effectively target the injected Fe3O4 NPs to GLUT1-positive tumor cells in infantile hemangioma.

Roles of Polycaprolactone Membrane on Guided Bone Formation in High-Speed Distraction of Experimental Design Cranium.

BACKGROUND: The aim of this research was to investigate whether covering of the distracted cranial bone segment with a polycaprolactone (PCL) membrane (guided bone formation) would accelerate the process of osteogenesis in high-speed distraction of adult rabbit. METHODS: Eighteen 24-weeks old, 3.0 to 3.5  kg, male New Zealand rabbits underwent routine gradual cranium distraction (group 1), distraction at high speed without the membrane (group 2), and distraction at high speed with a PCL membrane covering the cranium at the distraction gap (group 3). Five days after the cranial osteotomy, the distraction process was initiated at 3  mm per day (1.5  mm twice a day) in group 2 and group 3, and 1  mm per day (0.5  mm twice a day) in group 1 until 10  mm of length gain was achieved. At the consolidation 4 and 6 weeks, the bone mineral density was analyzed by a computerized tomography imaging protocol. The bone formation ratio of each group was compared with Hematoxylin and Eosin stain. The collagen formation of each group was analyzed by Massons' trichrome staining. RESULTS: Radiographic imaging and quantitative data indicated a significant increase in bone mineral density in group 1 and group 3 compared with group 2. Bone formation ratio in histologic analysis showed an increase in group 1 and group 3. Collagen synthesis in group 2 was significantly increased in distraction gap. In group 3, collagen fibers were significantly decreased underneath the PCL membrane. CONCLUSIONS: Polycaprolactone membrane covering the bone distraction gap provides an environment for faster bone formation in high-speed distraction.

Anthocyanins from black soybean seed coat enhance wound healing.

Anthocyanins are known to have antioxidant and antiinflammatory effects. We hypothesized that anthocyanins would enhance wound healing in Sprague-Dawley rats. The purpose of this study was to evaluate our hypothesis and investigate the mechanism of wound healing enhancement. The cytoprotective effect of an immortalized epidermal keratinocyte cell line (HaCaT) and human neonatal dermal fibroblasts in response to various concentrations of anthocyanins was determined. Vascular endothelial growth factor (VEGF) and thrombospondin 1 (TSP1) of HaCaT were measured by Western blot analysis. Anthocyanins were applied to the wounds in rats, and the healing ratio was calculated. Tissue VEGF, TSP1, CD31, nuclear factor-κB, and phosphorylation of IκBα were measured. The viability of the HaCaT cell line and human neonatal dermal fibroblasts increased under cytotoxicity by H2O2 in the anthocyanin-treated groups. The VEGF in the anthocyanin-treated groups increased, whereas TSP1 decreased. Wounds in the experimental groups healed faster, and VEGF and CD31 increased in the experimental groups, whereas TSP1 decreased. Anthocyanins inhibited the translocation of nuclear factor-κB (p65) from cytosol to nucleus and also prevented the phosphorylation of IκBα. Anthocyanins enhance wound healing through a cytoprotective effect, enhancement of angiogenesis, and an antiinflammatory effect.

Skin-redraping epicanthoplasty combined with the modified Hotz procedure to treat recurrent trichiasis in adults caused by congenital entropion.

OBJECTIVE: To report the efficacy of skin-redraping epicanthoplasty combined with the modified Hotz procedure for the management of recurrent trichiasis in adults caused by congenital entropion. METHODS: A retrospective chart review of nine recurrent trichiasis patients caused by congenital entropion was performed. All the patients were adults, and the follow-up period lasted more than 6 months. Success was defined as no recurrence of the trichiasis. RESULTS: The mean age of the patients was 22.7 ± 2.83 years, and the mean period of follow-up was 10.8 ± 4.15 months. The complete correction of trichiasis was observed in all patients, and there was no recurrence during the follow-up period. The ratio of the medial sclera area to the cornea area was enhanced from 0.25 ± 0.08 to 0.37 ± 0.11. Preoperatively, five patients were categorized as grade 2, and four patients were categorized as grade 3 of the Taylor classification, and all the patients were categorized as grade 0 after surgery. The preoperative severity of keratopathy was grade 3 in six patients and grade 2 in three patients. The preoperative lower lid horizontal skin fold heights were class 4 in six patients and class 3 in three patients. All the patients were grade 0 and class 1 after surgery. CONCLUSION: Skin-redraping epicanthoplasty combined with the modified Hotz procedure is reasonably successful in managing recurrent trichiasis in adults.

Anti-inflammatory effects of anthocyanins from black soybean seed coat on the keratinocytes and ischemia-reperfusion injury in rat skin flaps.

Ischemia-reperfusion injury is a phenomenon that occurs when tissues are subjected to ischemia for a variable period of time, and then reperfused. Inflammatory reaction has been implicated as one of the most important mechanism of ischemia-reperfusion injury. The purpose of this study was to evaluate the anti-inflammatory effects of anthocyanins from black soybean seed coat on keratinocytes in vitro and ischemia-reperfusion injury in vivo. We investigated the inhibition, by anthocyanins, of the expression of various inflammatory genes associated with ischemia-reperfusion injury in the tumor necrosis factor-alpha-treated (TNF-α) immortalized epidermal keratinocyte cell line (HaCaT). We also investigated the effects of anthocyanins on the survival of skin flaps after ischemia-reperfusion injury in the rats. According to Western blot analysis and a luciferase activity assay, anthocyanins inhibited TNF-α-induced intercellular adhesion molecule-1 and cyclooxygenase-2 (COX-2) levels through the NF-κB-dependent pathway. Administration of anthocyanins (50 and 100 mg/kg) significantly improved the flap area survival in the 10-hour ischemic model from 62% to 74.5% and 83%, respectively (P = 0.001). The related cytokines in skin flap also changed as the same pattern as in vitro. Our results indicate that anthocyanins from black soybean seed coat had anti-inflammatory effects on the HaCaT cell line and increase the survival of skin flaps through anti-inflammatory properties against ischemia-reperfusion injury.

Full-thickness lower eyelid defect reconstruction using a pedicle rotation temporal flap and Acellular Human Dermis Graft (Alloderm).

The aim of this research was to prospectively examine the combination of a pedicled temporal rotation flap with an acellular human dermal graft technique for intermediate-sized lower eyelid defect reconstruction. Pedicled temporal rotation flaps based on the orbicularis oculi muscle were used to reconstruct the anterior lamella of lower eyelid defects in six patients (five males and one female) while the posterior lamella was reconstructed using an acellular human dermis graft (Alloderm). Flap survival at 6 months was 100%. The functionality and cosmetic results of the technique were evaluated, and corneal protection was achieved. The texture and color of the reconstructed eyelid matched the surrounding skin, and neither pain nor corneal irritation was reported. The donor site scar healed well and was inconspicuous in all cases. Furthermore, no recurrence of malignancy was observed. The combination of a temporal rotational flap with an acellular human dermal graft is the key points. This technique could be ideal for the reconstruction of intermediate-sized full-thickness lower eyelid defects.

An anatomical study of the saphenous nerve, artery, and artery perforators within the thigh using cadaveric dissection.

Although the saphenous flap has been used in reconstruction as a free flap, there has not yet been an anatomic study about the perforators of the saphenous artery. The aim of this study is to investigate the anatomy of the saphenous artery and the number and locations of its perforators. We dissected parts of 10 legs from 5 cadavers. Measurements of the positions of the dissected saphenous arteries and their perforators were taken from the medial epicondyle of the femur. We observed the origin, end point, and the diameter of each of the arteries, and we investigated the numbers and locations of both septocutaneous and musculocutaneous perforators. The average length of saphenous artery was 14.8 cm, and it was located 12.0 cm above the medial epicondyle of the femur. The average diameter was 1.63 mm. A median average of 4 perforators branched out from a single saphenous artery. There was a median average of 2 septocutaneous perforators and 2 musculocutaneous perforators from the saphenous artery. The perforators were mainly located at 7 cm proximal to the medial epicondyle of the femur. The saphenous artery has many perforators and is therefore useful as the pedicle of the perforator flap. The saphenous artery perforator flap can be designed within 7 cm proximal to the medial epicondyle of the femur. Our results may be helpful in the applications of the neurocutaneous flap using the saphenous artery or the perforator flap based on septocutaneous perforators.

Reconstruction of defects after excision of facial skin cancer using a venous free flap.

After extensive excision of skin cancer on the face, or when skin cancer is located on the 3-dimensional structures of the face, reconstruction with a local flap can be impossible, or clinicians are reluctant to reconstruct defects with a skin graft because of postoperative contraction, hyperpigmentation, or other complication. Instead, an arterialized venous free flap can be used as an alternative method of reconstruction to prevent distortion and recurrence. Eight patients underwent surgery with an arterialized venous-free flap. We evaluated the cosmetic results using ordinary scale methods on the basis of 4 categories (color, contour, texture, and distortion of surrounding structures) and recurrence and metastases of skin cancer physically. The follow-up period ranged between 24 and 48 months, with an average of 33 months. All of the soft-tissue defects made by excising the tumor were reconstructed with good outcomes, except for 1 case. Regarding the cosmetic evaluation, the color was fair, the contour and texture were good, absence of distortion of surrounding structures was excellent, and the overall results in most all cases were good. There were no recurrences or metastases during the follow-up period. The arterialized venous free flap is an alternative plan among several reconstruction methods when skin cancer on the face is extensively excised.

Use of phosphodiesterase type 5 inhibitors and risk of melanoma: a meta-analysis of observational studies.

BACKGROUND: Phosphodiesterase type 5 inhibitor (PE5i) administration may stimulate the proliferation and survival of melanocytes. However, discrepancies remain regarding the association between PDE5i use and melanoma risk in observational studies in humans. AIM: To evaluate the association between PDE5i use and melanoma in a meta-analysis. MATERIALS AND METHODS: Studies were identified by searching the PubMed and Embase databases. A random-effects model was applied to synthesize the data. A stratified study was performed to evaluate the influence of study characteristics on outcomes. RESULTS: Four prospective cohort studies and three case-control studies with 1,534,615 male participants and 16,053 melanoma cases were incorporated. Patients who received a PDE5i had a significantly increased risk for melanoma (adjusted risk ratio [RR] =1.12, 95% CI =1.03-1.33, P=0.008) with moderate heterogeneity (I2=54%). Cohort studies (adjusted RR =1.22, 95% CI =1.02-1.46, P=0.03) largely contributed to this result rather than case-control studies. Subsequent stratified analyses revealed that sildenafil was associated with an increased risk of melanoma (adjusted RR =1.26, 95% CI =1.07-1.50, P=0.007), but tadalafil and vardenafil were not. Also, PDE5i use was associated with a significantly increased risk of in situ melanoma (adjusted RR =1.31, 95% CI =1.01-1.69, P=0.04), but not of localized or nonlocalized melanoma. CONCLUSION: PDE5i use may be associated with a significantly increased risk for melanoma in men. However, further research is needed to determine whether the association is causative.

Chaetocin induces apoptosis in human melanoma cells through the generation of reactive oxygen species and the intrinsic mitochondrial pathway, and exerts its anti-tumor activity in vivo.

Chaetocin is a small-molecule natural product produced by Chaetomium species fungi, and it has a potent anti-proliferative pharmacological activity on various cancer cells. However, the effect of chaetocin on anti-melanoma pharmacological role has not been investigated. Therefore, in this study, we explored the effect of chaetocin on cell proliferation in the human melanoma Sk-Mel-28 and A375 cells and the growth of tumor xenografts in nude mice. The results indicated that chaetocin treatment significantly suppressed cell proliferation and induced apoptosis in the Sk-Mel-28 and A375 cells in a dose- and time-dependent manner. Furthermore, chaetocin treatment resulted in an increased level of cellular reactive oxygen species (ROS), and pre-incubation of cells with N-acetylcysteine (NAC) significantly abrogated chaetocin-induced apoptosis in the melanoma cells. A significant reduction of mitochondrial membrane potential and the release of cytochrome c were observed after chaetocin treatment. Additionally, chaetocin treatment significantly up-regulated the protein levels of Bax, cleaved caspase-9/-3, simultaneously down-regulated the protein levels of Bcl-2, procaspase-9/-3, and activated caspase-9/-3 activity in the melanoma cells. The in vivo data demonstrated that chaetocin treatment significantly inhibited the growth of melanoma tumor xenografts in nude mice, which was closely associated with apoptosis induction, a reduced level of PCNA (proliferating cell nuclear antigen) expression, and activation of capase-9/-3 in tumor xenografts. These are the first data to demonstrate that chaetocin exerts a proapoptotic activity on human melanoma cells through ROS generation and the intrinsic mitochondrial pathway. Therefore, chaetocin might represent an effective candidate for melanoma chemotherapy.

[Advanced orbicularis oculi muscle flap for eyelid defect].

OBJECTIVE: To investigate the application and therapeutic effect of advanced orbicularis oculi muscle (OOM ) flap for eyelid defect. METHODS: Uni-pedicle or bi-pedicle advanced OOM flaps were designed according to the location, depth and size of the eyelid defects. The resulted wounds in the donor sites were closed directly. The flap size ranged from 1.5 cm x 0.5 cm - 6.0 cm x 3.5 cm. RESULTS: 120 cases were treated. All the flaps survived except for 3 flaps with epidermis necrosis at the end of flaps, which healed after dressing. The patients were followed up for 3 -36 months with inconspicious scar in donor sites. The flap color, texture had a good match with surrounding skin. CONCLUSIONS: The OOM flap is ideal for eyelid defect with reliable blood supply, satisfied color and texture. The wound at donor site can be closed directly with less morbidity.

Photodynamic therapy suppresses tumor growth in an in vivo model of human hemangioma.

The authors investigated the efficacy of photodynamic therapy against infantile hemangioma using a hemangioma animal model. Eighty-three hemangioma specimens from five children were implanted into nude mice. The gross and volume changes of the implants were evaluated for up to 13 weeks. The histological change of the implant was evaluated at 5 weeks after transplantation. Photodynamic therapy was performed between 6 and 10 weeks after transplantation. The photosensitizer uptake of the implant was evaluated at 24 h after photosensitizer administration. The implant response was evaluated at 0, 12, and 24 h after light delivery. The change in ATF3 levels, a transcription factor induced under severe hypoxic conditions, was investigated immediately after treatment. The implant volume increased slowly during the first 4 weeks and then involuted. At 5 weeks after transplantation, plump endothelial cells formed tightly packed sinusoidal channels, and the endothelial cells were positive for CD31 and GLUT1 expression. At 24 h after photosensitizer administration, confocal analysis showed that the photosensitizer was present within CD31-positive cells. The implant volume was significantly decreased in the treated implants compared with the untreated implants (p < 0.0001). At 24 h after light delivery, most cells had collapsed. ATF3 expression increased gradually and then reached a maximum level at 4 h after treatment. Photodynamic therapy was effective in the treatment of infantile hemangioma. Apoptosis, a major mechanism of hemangioma destruction in the early phase, might be caused by ischemic injury as well as direct effects of photodynamic therapy.

Regeneration of peripheral nerves by transplanted sphere of human mesenchymal stem cells derived from embryonic stem cells.

In cell therapy, the most important factor for therapeutic efficacy is the stable supply of cells with best engraftment efficiency. To meet this requirement, we have developed a culture strategy such as three-dimensional sphere of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) in serum-free medium. To investigate the in vivo therapeutic efficacy of hESC-MSC spheres in nerve injury model, we transected the sciatic nerve in athymic nude mice and created a 2-mm gap. Transplantation of hESC-MSC as sphere repaired the injured nerve significantly better than transplantation of hESC-MSC as suspended single cells in regard to 1) nerve conduction (sphere; 28.81 ± 3.55 vs. single cells; 18.04 ± 2.10, p < 0.05) and 2) susceptibility of nerve stimulation at low voltage (sphere; 0.38 ± 0.08 vs. single cells; 0.66 ± 0.11, p < 0.05) at 8 weeks. Recovery after sphere transplantation was near-complete when compared with the data of normal control (sphere 28.81 ± 3.55 vs normal 32.62 ± 2.85 in nerve conduction : sphere 0.38 ± 0.08 vs normal 0.36 ± 0.67 in susceptibility of nerve stimulation, no significant difference, respectively). Recovery in function of the injured nerve was well corroborated by the histologic evidence of regenerated nerve. In the mechanistic analysis, the supernatant of sphere-forming hESC-MSC contains hepatocyte growth factor and insulin-like growth factor-binding protein-1 significantly more than the supernatant of the single cells of hESC-MSC has, which might be the key factors for the improved engraftment efficiency and greater regeneration of injured peripheral nerve.