The Value of Anterolateral Thigh Free Flap for the Reconstruction of Malignant Melanoma of the Sole of the Foot.

BACKGROUND: Wide excision of malignant melanoma on the foot usually results in an extensive function-destroying defect, and the reconstruction of foot defects remains challenging for reconstructive surgeons. We propose using anterolateral thigh perforator (ALT) free flaps for the reconstruction of widespread defects caused by malignant melanoma in the sole. METHODS: This retrospective study included 34 patients who underwent reconstruction of sole defects caused by malignant melanoma resection with 35 ALT perforator free flaps between August 2005 and July 2021. RESULTS: In total, 18 male patients and 16 female patients were included (mean age at surgery, 65.4 years). The mean size of the flaps was 100.4 cm 2 . Thirty-three of the 35 flaps survived. Hematoma, seroma, and chronic ulceration were not identified in any cases. All patients achieved independent ambulation within the follow-up period, except 1 patient with gait discomfort. The 5-year overall and disease-free survival rates of patients were 64.4% and 56.6%, respectively. CONCLUSIONS: The ALT flap is a versatile surgical option that should be considered for reconstruction of the sole after malignant melanoma resection, considering its various surgical advantages and the functional aspects of independent ambulation, the aesthetic aspects of wearing conventional footwear, and the anatomical aspects of the sole.

Analysis and Guidelines for Revisional Malarplasty; Most Common Facial Skeletal Contouring Surgery.

BACKGROUND: Revisional malarplasty is the most frequently performed and difficult to perform revision surgery among facial contouring surgeries. The incidence of postoperative complications and need for revision surgery is increasing because of indiscriminate malar reduction through a narrow surgical space. The authors analyzed cases of revisional malarplasty secondary to complications. METHODS: The authors analyzed the time required and technique used in 172 patients who underwent revisional malarplasty in the past 3 years. The incision made for the approach and the graft material used for reconstruction were also investigated. RESULTS: Of 172 patients, 35 (20.3%) underwent emergency revision. Furthermore, 71 (41.2%) required an intraoral incision, and 101 (58.8%) required a coronal incision. A total of 81(47.1%) patients required artificial or autogenous bone grafts. CONCLUSIONS: Patients with failed malarplasty should receive immediate intervention to prevent functional and cosmetic problems. When bone resorption occurs due to unfavorable union or nonunion, reconstruction using appropriate autologous tissue can prevent functional impairment and long-term cosmetic problems.

Results of Lip Adhesion in Wide Unilateral Complete Cleft Lip Patients.

ABSTRACT: Long-term follow-up results of many surgical techniques for lip adhesion are unavailable. Thus, we report the surgical results of patients who underwent lip adhesions performed by a single surgeon. We retrospectively analyzed two-dimensional photographs of 29 patients aged 1 year who underwent lip adhesion and definite lip repair. Among these patients, we analyzed the photographs of 20 patients aged 6 years who underwent secondary rhinoplasty. The ratio of the cleft side length to the noncleft side length was calculated. Only the upper lip length in the photographs of 1-year-olds was measured; both the upper lip and nose lengths were measured in the photographs of 6-year-olds. Lip width, vermilion height, and medial lip height on the cleft and non-cleft sides of 1-year-olds were not significantly different; the alar base width ratio was 1.17 ±â€Š0.15, and the lateral lip height ratio was 0.91 ±â€Š0.09 (P < 0.001). No significant differences were observed in lip width and vermilion height between the cleft and non-cleft sides of the upper lip of 6-year-olds; the alar base width ratio was 1.22 ±â€Š0.16, medial lip height ratio was 1.11 ±â€Š0.11, and lateral lip height ratio was 0.89 ±â€Š0.09 (P < 0.05). There were no significant differences in the alar projection and nasal dome height on the cleft side of the nose; the nostril height and width ratios were 0.82 ±â€Š0.11 and 1.31 ±â€Š0.21 (P < 0.001), respectively. These consecutively performed lip adhesions for patients with wide unilateral complete cleft lip resulted in excellent long-term results. Therefore, lip adhesion for wide unilateral complete cleft lip is a reasonable alternative to presurgical molding.

A Study on the Effective Ratio of Fat to Stromal Vascular Fraction for Cell-Assisted Lipotransfer.

BACKGROUND: Fat grafting, used for soft tissue augmentation during aesthetic or reconstructive plastic surgery, has disadvantages of low efficiency and unpredictable resorption rate. As an alternative, cell-assisted lipotransfer (CAL) is widely used because of its simplicity and low fat resorption rate. However, relevant studies on optimal CAL parameters are still lacking. Here, we aimed to identify the most effective ratio of fat to stromal vascular fraction (SVF) for CAL. METHODS: We designed two experimental paradigms. The first involved four groups of mice, each group injected with varying ratios of fat and SVF purified from different amounts of fat from a fixed amount of harvested fat. The second experiment involved four groups of mice, each injected with varying amounts of SVF mixed with a fixed amount of fat tissue. The amount of surviving fat in both experiments was compared 8 weeks after fat transplantation. RESULTS: In the first experiment, the group injected with only fat, without consuming any of the harvested fat for SVF purification, showed the greatest mean volume and weight. In the second experiment, groups with 1:1 or more ratio of fat to SVF showed greater volume and weight than the group without SVF. Notably, a ratio of 1:1 did not give significantly different results than higher ratios. CONCLUSIONS: Thus, when a limited amount of fat tissue is available, using all of it for grafting is the most effective. However, if an adequate amount is available, using a fat-to-SVF ratio of 1:1 is the most efficient. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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.

Usefulness of Microfat Grafting in Patients With Repaired Cleft Lip.

In many patients, the volume of the upper lip is deficient after cleft lip repair operation. However, there is no well-established procedure to correct this volume deficiency. In the present study, the authors attempted to increase the overall three-dimensional volume of the upper lip in repaired cleft lip patients with upper lip volume deficiency through autogenous microfat grafting. Thirty patients with upper lip volume deficiency after cleft lip repair underwent fat grafting in the upper lip from November 2007 to March 2015. Among these patients, postoperative outcome was evaluated in 15 patients using 2 methods for the evaluation. One method involved measuring the change in the shape of lips using pre- and postoperative photographs, and the other involved investigating the levels of satisfaction with the surgical results by distributing a scoring questionnaire to patients, doctors, and the general public. The ratio of upper lip protrusion relative to the lower lip increased by 46.71% on average after operation, and the sum of the vermilion heights increased by 31.68% on average. In the survey of satisfaction levels, patients, plastic surgeons, and the general public gave mean scores of 3.80, 3.91, and 4.03, respectively. When volume deficiency of the upper lip is present in repaired cleft lip patients, correction using autogenous microfat grafting is believed to be effective.

Effects of human adipose-derived stem cells and stromal vascular fraction on cryopreserved fat transfer.

BACKGROUND: The use of cryopreserved adipose tissue for soft tissue augmentation is common, but unpredictability of fat graft viability remains a limitation. Adipose-derived stem cell (ADSC) and stromal vascular fraction (SVF) have been introduced to enhance viability and improve the survival of transplanted fat tissue. OBJECTIVE: To investigate whether supplementation with ADSC or SVF improved the survival of cryopreserved fat grafts. METHODS: The cryopreserved fat grafts were treated with ADSC, SVF, or normal saline in 30 six-week-old male nude mice to test whether ADSC and SVF could improve the survival of the transplanted fat tissue. The authors examined the weight, volume, and histological features of each group (n = 10) at 8 weeks after transplantation to evaluate the survival of the fat tissue. RESULTS: There was no difference between the control and SVF groups with respect to weight, volume, and histological findings. However, the ADSC group showed a significant increase in weight and volume compared with the control and SVF groups. Histological examination showed that the ADSC supplementation improved the quality of the transplanted fat grafts. CONCLUSION: Taken together, these results suggest a potential clinical utility of ADSC but no advantage of SVF in facilitating cryopreserved fat transfer.

Extent of palatal lengthening after cleft palate repair as a contributing factor to the speech outcome.

Operative techniques in performing cleft palate repair have gradually evolved to achieve better speech ability with its main focus on palatal lengthening and accurate approximation of the velar musculature. The authors doubted whether the extent of palatal lengthening would be directly proportional to the speech outcome. Patients with incomplete cleft palates who went into surgery before 18 months of age were intended for this study. Cases with associated syndromes, mental retardation, hearing loss, or presence of postoperative complications were excluded from the analysis. Palatal length was measured by the authors' devised method before and immediately after the cleft palate repair. Postoperative speech outcome was evaluated around 4 years by a definite pronunciation scoring system. Statistical analysis was carried out between the extent of palatal lengthening and the postoperative pronunciation score by Spearman correlation coefficient method. However, the authors could not find any significant correlation. Although the need for additional research on other variables affecting speech outcome is unequivocal, we carefully conclude that other intraoperative constituents such as accurate reapproximation of the velar musculature should be emphasized more in cleft palate repair rather than palatal lengthening itself.

Modified Palatoplasty Method (Busan Modification) for Incomplete Type Cleft Palate.

To achieve ultimate goals of cleft palate repair, levator muscle's appropriate reapproximation is viewed more importantly as of now, rather than simple palatal lengthening. Authors have developed modified version of 2-flap palatoplasty technique for incomplete type cleft palate and conducted follow-up study, including its early complications, speech evaluation, and facial growth measurement. Of the entire patients receiving a surgery from 2002 to 2012, the authors surveyed consecutive 100 cases of nonsyndromic incomplete cleft palate receiving our modified surgeries, and their early postoperative complication occurrence and the progress were monitored. Of them, the authors performed speech evaluation (n = 36) and facial growth measurement (n = 28) for the patients who the authors could follow-up until at least the age of 4.The medical record review has found no single, early postoperative complication requiring immediate treatment. A total of 10 cases showed delayed wound healing, but 7 of them recovered without a special problem and the other 3 showed residual fistula, recording 3% fistula formation rate. Of the 36 pronunciation evaluation cases, average score was 64.2, reaching almost to the full score of 66, but 1 case with the lowest point was found to need a corrective surgery for the clinical velopharyngeal dysfunction. Cephalometric measurement receiving 28 cases showed sella-nasion-A point angle (SNA) of 82.8° ± 3.4°, sella-nasion-B point angle (SNB) of 78.9° ± 3.9°, and a point-nasion-B point angle (ANB) of 3.9°â€Š±â€Š1.9°. In all range of the measurements, no significant statistical difference was found between normal population at that age and the sample group. The authors consecutively performed this modified method (Busan modification) for patients with incomplete cleft palate and consequentially found a lower rate of early postoperative complications. Moreover, relatively excellent long-term results including speech evaluation score and facial growth outcome were proved during 4 years of postoperative follow-up period.

miR-137 controls proliferation and differentiation of human adipose tissue stromal cells.

BACKGROUND/AIMS: Demonstrating the molecular mechanisms of human adipose tissue-derived mesenchymal stem cells (hADSCs) differentiation and proliferation could develop hADSCs-based cell therapy. METHODS: The microRNA-137 (miR-137) and cell division control protein 42 homolog (CDC42) levels were regulated by oligonucleotides transfection. The adipogenic differentiation was induced for 10 days in an adipogenic medium and assessed by using an Oil Red O stain. The regulation of miR-137 on CDC42 expression was determined by western blot, real-time PCR and luciferase reporter assay. RESULTS: We confirmed the roles of miR-137 on hADSCs proliferation and adipogenic differentiation. We showed that overexpression of miR-137 inhibited both hADSCs proliferation and adipogenic differentiation. Overexpression of miR-137 also downregulated protein and mRNA levels of CDC42, a predicted target of miR-137. In contrast, inhibition of miR-137 with 2'-O-methyl antisense RNA increased proliferation and adipogenic differentiation in hADSCs. Luciferase reporter activity in the miR-137 target site within the CDC42 3'UTR was lower in miR-137-transfected hADSCs than in control miRNA-transfected hADSCs. RNA interference-mediated downregulation of CDC42 in hADSCs inhibited their proliferation and adipogenic differentiation. CONCLUSION: Our results indicate that miR-137 regulates hADSCs adipogenic differentiation and proliferation by directly targeting CDC42. These findings improve our knowledge of the molecular mechanisms governing hADSCs differentiation and proliferation.

BMP2 increases adipogenic differentiation in the presence of dexamethasone, which is inhibited by the treatment of TNF-α in human adipose tissue-derived stromal cells.

BACKGROUND/AIMS: The aim of this study was to analyze the effect of BMP2 on osteogenic differentiation of human adipose tissue-derived stromal cells (hADSCs). METHODS: Cultured cells were differentiated into osteogenic lineage in the presence of BMP2. Gene expressions were determined by real time PCR. RESULTS: BMP2 increased (2/8) or inhibited (6/8) osteogenic differentiation according to hADSCs batches. Regardless of the BMP2 action on osteogenic differentiation, BMP2 induced lipid droplet formation under an osteogenic differentiation condition in all batches of hADSCs, not hBMSCs, to be tested, which was confirmed by analysis of adipogenesis related genes expression. hADSCs expressed various BMP receptors. BMP2 increased expression of BMP2-responsive genes such as DLX3 and ID2, and induced SMAD1 phosphorylation in hADSCs and hBMSCs. BMP2 increased osteogenic differentiation of hADSCs in osteogenic medium in which dexamethasone was omitted. The addition of BMP2 in the control culture media containing dexamethasone alone lead to formation of lipid droplets and increased C/EBP-α expression in hADSCs. In the presence of TNF-α, BMP2 stimulated osteogenic differentiation of hADSCs even in hADSCs batches in which treatment of BMP2 alone inhibited osteogenic differentiation. CONCLUSION: These data indicate that the control of osteogenesis and adipogenesis in hADSCs is closely related, and that hADSCs have preferential commitment to adipogenic lineages.

Perioperative management of facial reconstruction surgery in patients with end-stage renal disease undergoing dialysis.

BACKGROUND: The rising incidence of dialysis-dependent end-stage renal disease (ESRD) has underscored the need for collaboration between plastic surgeons and nephrologists, particularly concerning preoperative and postoperative management for facial reconstruction. This collaboration is essential due to a scarcity of comprehensive information in this domain. METHODS: A study initiated in January 2015 involved 10 ESRD cases on dialysis undergoing Mohs micrographic surgery for facial skin cancer, followed by reconstructive surgery under general anesthesia. To ensure surgical safety, rigorous measures were enacted, encompassing laboratory testing, nephrology consultations, and preoperative dialysis admission. Throughout surgery, meticulous control was exercised over vital signs, electrolytes, bleeding risk, and pain management (excluding nonsteroidal anti-inflammatory drugs). Postoperative assessments included monitoring flap integrity, hematoma formation, infection, and cardiovascular risk through plasma creatinine levels. RESULTS: Adherence to the proposed guidelines yielded a notable absence of postoperative wound complications. Postoperative plasma creatinine levels exhibited an average decrease of 1.10 mg/dL compared to preoperative levels, indicating improved renal function. Importantly, no cardiopulmonary complications or 30-day mortality were observed. In ESRD patients, creatinine levels decreased significantly postoperatively compared to the preoperative levels (p< 0.05), indicating favorable outcomes. CONCLUSION: The consistent application of guidelines for admission, anesthesia, and surgery yielded robust and stable outcomes across all patients. In particular, the findings support the importance of adjusting dialysis schedules. Despite the limited sample size in this study, these findings underscore the effectiveness of a collaborative and meticulous approach for plastic surgeons performing surgery on dialysis-dependent patients, ensuring successful outcomes.

Incidence of Velopharyngeal Insufficiency after Primary Cleft Palate Repair: A 27-Year Assessment of One Surgeon's Experience.

Background Velopharyngeal insufficiency (VPI) is a major complication of cleft palate repair. The purpose of this study was to evaluate the incidence and predictive factors of VPI after cleft palate repair based on 27 years of one surgeon's experience. Methods Medical records were retrospectively reviewed for 652 patients who underwent cleft palate repair between 1995 and 2021. After exclusion of those with other syndromes or developmental disorders, the study included 374 patients with sufficient follow-up until the age of 4 years, when language evaluation was possible. VPI status was categorized through subjective and objective tests into normal, VPI, and borderline. We analyzed potential differences in VPI incidence by multiple factors. Factors with significance were analyzed to confirm the relationships between subvariables. Results Of the 374 patients, 311 (83.2%) exhibited normal pronunciation, 51 (13.6%) had VPI, and 12 (3.2%) were borderline. Primary cleft palate repair performed after 18 months was associated with a higher incidence of VPI than repair conducted before 18 months ( p = 0.005). The incidence of VPI was higher in cases of submucous cleft palate than in the other types based on the Veau classification ( p = 0.011). However, in the multivariable analysis, only the submucous type showed statistically significant results ( p = 0.026). Conclusion A total of 374 people underwent primary cleft palate repair, and 13.6% of those with VPI required secondary therapy. The incidence of VPI was relatively high among patients with primary cleft palate repair after 18 months and patients with submucous cleft palate.

Impact of anatomical abnormalities on velopharyngeal insufficiency in patients with submucous cleft palate.

BACKGROUND: Submucous cleft palate (SMCP) is a congenital anomaly characterized by the presence of Calnan's triad. However, in clinical practice, it is common for individuals to exhibit one or two anatomical abnormalities within the triad. Furthermore, the definition of SMCP has been diverse and ambiguous in literature. Therefore, this study aimed to analyze the correlation between anatomical abnormalities and development of velopharyngeal insufficiency (VPI). METHODS: We conducted a retrospective analysis of 99 patients referred to our clinic for speech issues or anatomical abnormalities identified during routine oral examinations from January 2012 to June 2023. A single surgeon performed all physical examinations. We evaluated the presence of bony notch, zona pellucida, and bifid uvula, assigned a score to each abnormality, and analyzed their correlation with VPI. The correlation of each of the abnormalities with VPI development was examined, along with the relationship between the number of abnormalities and VPI. RESULTS: Among the 99 patients, 27 were diagnosed with VPI. Only the bony notch had a significant correlation with VPI development. The incidence of VPI tended to increase with the presence of more anatomical abnormalities. VPI occurred in approximately 40% of patients exhibiting all three anatomical abnormalities. CONCLUSION: The study findings highlight the importance of meticulous intraoral examinations in patients with SMCP and careful monitoring of patients with a bony notch or two or more anatomical abnormalities.

Transdermal scopolamine for the treatment of recurrent parotid sialocele: a case report.

Recurrent parotid sialocele is rare and challenging to treat. Treatment options are limited for cases of parotid sialocele that recur despite ductal ligation. This case study presents a patient who underwent wide excision of the right buccal mucosa due to squamous cell carcinoma. During the wide excision, a segment of the parotid duct was excised, and ductal ligation was performed to prevent the occurrence of a sialocele, followed by reconstruction using a folded anterolateral thigh free flap. Twenty-two days after surgery, parotid sialocele occurred despite the initial ductal ligation and subsequent ductal ligation was performed; however, the sialocele recurred. As an alternative therapeutic option, a transdermal scopolamine patch was applied for 3 weeks, with one patch used every 3 days. The results were encouraging, with complete resolution of the sialocele. A transdermal scopolamine offers a noninvasive, convenient method of treating parotid sialocele with minimal side effects. The successful outcome of this case suggests that a transdermal scopolamine can be an effective therapeutic option for recurrent parotid sialocele in conjunction with surgical treatment.

Appropriate Surgical Margins for Excision of Squamous Cell Carcinoma of the Lower Lip.

Background Squamous cell carcinoma (SCC) is the most common malignancy on the lower lip. Surgical excision, the standard treatment for SCC, requires full-thickness excision. However, no consensus exists about the appropriate surgical margin. Therefore, we investigated the appropriate surgical margin and excision technique by analyzing 23 years of surgical experience with lower-lip SCC. Methods We reviewed 44 patients with lower-lip SCC who underwent surgery from November 1997 to October 2020. Frozen biopsy was performed with an appropriate margin on the left and right sides of the lesion, and the margin below the lesion was the skin above the sulcus boundary. If the frozen biopsy result was positive, an additional session was performed to secure a negative margin. Full-thickness excision was performed until the final negative margin. In each patient, the total number of sessions performed, final surgical margin, and recurrence were analyzed. Results Forty-one cases ended in the first session, 2 ended in the second session, and 1 ended in the third session. The final surgical margins (left and right; n = 88) were 5 mm (66%), 7 mm (9%), 8 mm (2.3%), 10 mm (20.4%), and 15 mm (2.3%). During an average follow-up of 67.4 months (range, 12-227 months), recurrence occurred in one patient. Conclusion The final surgical margin was 5 mm in 66% (58/88) of the cases, and 97.7% (86/88) were within 10 mm. Therefore, we set the first frozen biopsy margin to 5 mm, and we suggest that a 5-mm additional excision is appropriate when frozen biopsy results are positive.

Effective resection of dermatofibrosarcoma protuberans using the novel Saturn's rings technique.

Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade sarcoma with locally infiltrative characteristics. A wide excision is made with a 5 cm gross margin. However, recently, Mohs micrographic surgery has emerged as an alternative. In this study, we evaluate a novel method (Saturn's Rings technique) for removing tumors that combines the advantages of wide excision and Mohs micrographic surgery. Between September 2001 and March 2020, 29 patients with DFSP, excluding the head and neck, were treated using Saturn's rings technique. Frozen biopsies were performed at regular intervals under various conditions and depths. If the biopsy was positive, a negative margin was obtained through an additional session. The depth and breadth of excision, reconstruction method, and postoperative recurrence were analyzed. The breadth of excision was evaluated at 1 cm intervals. Only 1 session was required in 12 cases, 2 sessions were needed in 13 cases, and 3 or more sessions were performed in 4 cases. In 24 cases, the depth of excision was limited to above the superficial fascia, with a negative biopsy of the superficial fascia. Local flaps were the most common reconstruction method (n = 21, 72.4%). No cases of recurrence were observed at follow-up (average, 45.7 months). Saturn's rings technique for DFSP maximized the preservation of normal tissue with minimal resection, was advantageous for reconstruction, and yielded good results without recurrence.

Lymphaticovenular anastomosis for Morbihan disease: a case report.

Morbihan disease (MD) is a very rare condition characterized by rosaceous or erythematous lymphedema on the upper twothirds of the face. A definitive management strategy for MD is lacking, and treatment is challenging. Herein, we present a case of persistent bilateral eyelid edema treated by lymphaticovenular anastomosis (LVA) and lymph node-vein bypass surgery. The patient experienced persistent bilateral eyelid edema. Indocyanine green lymphography was performed, and the diagnosis of bilateral facial lymphedema was confirmed. On the right side, a preauricular lymphatic vessel was anastomosed to a vein. On the left side, lymphostomy on the preauricular lymph node was done, with anastomosis to the transected proximal end of the concomitant vein of the transverse facial artery. Furthermore, a preauricular lymphatic vessel was anastomosed to a vein. Eyelid edema decreased and progressively improved on both sides. The outcome of this case suggests that LVA and lymph node-vein bypass surgery are appropriate for treating persistent eyelid edema related to MD.

MicroRNA 21 regulates the proliferation of human adipose tissue-derived mesenchymal stem cells and high-fat diet-induced obesity alters microRNA 21 expression in white adipose tissues.

A better understanding of the molecular mechanisms that govern human adipose tissue-derived mesenchymal stem cells (hASCs) differentiation could provide new insights into a number of diseases including obesity. Our previous study demonstrated that microRNA-21 (miR-21) controls the adipogenic differentiation of hASCs. In this study, we determined the expression of miR-21 in white adipose tissues in a high-fat diet (HFD)-induced obesity mouse model to examine the relationship between miR-21 and obesity and the effect of miR-21 on hASCs proliferation. Our study showed biphasic changes of miR-21 expression and a correlation between miR-21 level and adipocyte number in the epididymal fat of HFD mice. Over-expression of miR-21 decreased cell proliferation, whereas inhibiting miR-21 with 2'-O-methyl-antisense RNA increased it. Over-expression of miR-21 decreased both protein and mRNA levels of STAT3, whereas inhibiting miR-21 with 2'-O-methyl-antisense RNA increased these levels. The activity of a luciferase construct containing the miR-21 target site from the STAT3 3'UTR was lower in LV-miR21-infected hASCs than in LV-miLacZ infected cells. RNA interference-mediated down-regulation of STAT3 decreased cell proliferation without affecting adipogenic differentiation. These findings provide the evidence of the correlation between miR-21 level and adipocyte number in the white adipose tissue of HFD-induced obese mice, which provides new insights into the mechanisms of obesity.

miR-21 modulates tumor outgrowth induced by human adipose tissue-derived mesenchymal stem cells in vivo.

Mesenchymal stem cells (MSCs) have generated a great deal of interest in clinical situations, due principally to their potential use in regenerative medicine and tissue engineering applications. However, the therapeutic application of MSCs remains limited, unless the favorable effects of MSCs on tumor growth in vivo, and the long-term safety of the clinical applications of MSCs, can be more thoroughly understood. In this study, we determined whether microRNAs can modulate MSC-induced tumor outgrowth in BALB/c nude mice. Overexpression of miR-21 in human adipose-derived stem cells (hADSCs) inhibited hADSC-induced tumor growth, and inhibition of miR-21 increased it. Downregulation of transforming growth factor beta receptor II (TGFBR2), but not of signal transducer and activator of transcription 3, in hADSCs showed effects similar to those of miR-21 overexpression. Downregulation of TGFBR2 and overexpression of miR21 decreased tumor vascularity. Inhibition of miR-21 and the addition of TGF-ß increased the levels of vascular endothelial growth factor and interleukin-6 in hADSCs. Transplantation of miR-21 inhibitor-transfected hADSCs increased blood flow recovery in a hind limb ischemia model of nude mice, compared with transplantation of control oligo-transfected cells. These findings indicate that MSCs might favor tumor growth in vivo. Thus, it is necessary to study the long-term safety of this technique before MSCs can be used as therapeutic tools in regenerative medicine and tissue engineering.

Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia: a pilot study.

BACKGROUND: Treatment of critical limb ischemia (CLI) by bypass operation or percutaneous vascular intervention is occasionally difficult. The safety and efficacy of multiple intramuscular adipose tissue-derived mesenchymal stem cells (ATMSC) injections in CLI patients was determined in the study. METHODS AND RESULTS: The study included 15 male CLI patients with ischemic resting pain in 1 limb with/without non-healing ulcers and necrotic foot. ATMSC were isolated from adipose tissue of thromboangiitis obliterans (TAO) patients (B-ATMSC), diabetes patients (D-ATMSC), and healthy donors (control ATMSC). In a colony-forming unit assay, the stromal vascular fraction of TAO and diabetic patients yielded lesser colonies than that of healthy donors. D-ATMSC showed lower proliferation abilitythan B-ATMSC and control ATMSC, but they showed similar angiogenic factor expression with control ATMSC and B-ATMSC. Multiple intramuscular ATMSC injections cause no complications during the follow-up period (mean follow-up time: 6 months). Clinical improvement occurred in 66.7% of patients. Five patients required minor amputation during follow-up, and all amputation sites healed completely. At 6 months, significant improvement was noted on pain rating scales and in claudication walking distance. Digital subtraction angiography before and 6 months after ATMSC implantation showed formation of numerous vascular collateral networks across affected arteries. CONCLUSIONS: Multiple intramuscular ATMSC injections might be a safe alternative to achieve therapeutic angiogenesis in patients with CLI who are refractory to other treatment modalities.