Blind Curettage Technique for Treatment of Mucous Cysts Associated with Heberden Nodes: Description of Operative Technique.

The standard treatment for mucous cysts with Heberden nodes is excision of the dorsolateral osteophytes and capsule of the distal interphalangeal joint or thumb interphalangeal joint, including the stalk of the cyst. The skin incision varies for cases depending upon the geometry. We propose a surgical method utilizing blind lateral approaches for treating such mucous cysts.

Subtotal Second Toe Transfer for Finger Reconstruction after Malignant Fibroblastic Tumor Resection.

The transposition of an adjacent finger following the loss of a finger due to a malignant tumor resection improves hand function. However, patients may not accept the resulting appearance of a three-finger hand. A 28-year-old male with a malignant fibroblastic tumor at the base of the ring finger underwent resection of the tumor, excising the phalanx and a portion of the metacarpal. He refused a ray amputation and subsequent fifth-finger transposition. Therefore, we reconstructed the defect with a long-vascularized subtotal second toe from the metacarpal neck to the middle phalanx base of the fourth finger. There was no tumor recurrence, and the patient was highly satisfied with hand function and cosmetic appearance at 3 years of follow-up.

Novel predictive approaches for drug-induced convulsions in non-human primates using machine learning and heart rate variability analysis.

Drug-induced convulsions are a major challenge to drug development because of the lack of reliable biomarkers. Using machine learning, our previous research indicated the potential use of an index derived from heart rate variability (HRV) analysis in non-human primates as a biomarker for convulsions induced by GABAA receptor antagonists. The present study aimed to explore the application of this methodology to other convulsants and evaluate its specificity by testing non-convulsants that affect the autonomic nervous system. Telemetry-implanted males were administered various convulsants (4-aminopyridine, bupropion, kainic acid, and ranolazine) at different doses. Electrocardiogram data gathered during the pre-dose period were employed as training data, and the convulsive potential was evaluated using HRV and multivariate statistical process control. Our findings show that the Q-statistic-derived convulsive index for 4-aminopyridine increased at doses lower than that of the convulsive dose. Increases were also observed for kainic acid and ranolazine at convulsive doses, whereas bupropion did not change the index up to the highest dose (1/3 of the convulsive dose). When the same analysis was applied to non-convulsants (atropine, atenolol, and clonidine), an increase in the index was noted. Thus, the index elevation appeared to correlate with or even predict alterations in autonomic nerve activity indices, implying that this method might be regarded as a sensitive index to fluctuations within the autonomic nervous system. Despite potential false positives, this methodology offers valuable insights into predicting drug-induced convulsions when the pharmacological profile is used to carefully choose a compound.

Case Report of Gas Gangrene after Reconstructive Surgery with Anterolateral Thigh Flap for Resection of Oral Cancer.

Necrotizing fasciitis (NF) type I is an acute subcutaneous tissue infection that can promptly disseminate generating crepitus. If not accurately diagnosed and expeditiously treated, it becomes a life-threatening infection. In this report, we present a 65-year-old man who developed a case of NF after a hemiglossectomy resecting a tumor in the dorsal surface of the tongue. A biopsy was performed, and he was pathologically diagnosed with squamous cell carcinoma (T2N1M0). The patient underwent preoperative oral cleaning. Right hemiglossectomy was performed by cervical dissection, pull-through style, with tooth removal on the right mandible and a left anterolateral femoral flap reconstruction. Routine intraoperative lavage was performed with 2000 mL of saline solution. Cefazolin 1gr was administered two times per day postoperatively. Four days after primary surgery, the flap circulation was inadequate; therefore, a computed tomography scan was taken, which indicated gas in the ventral neck area. Tooth extraction was the suspected etiology. Debridement was performed; the abscess was drained and cultured, indicating the presence of Staphylococcus haemolyticus and Escherichia coli. It seems that the abscess was not formed by NF, but rather by leachate reservoir associated with the head and neck tumor. After debridement, re-reconstruction was performed with a deltopectoral flap and pectoralis major myocutaneous flap. When NF is present after a neck dissection, there is a risk of disruption due to the direct invasion and inflammation into the carotid artery. Therefore, it is important to provide adequate oral cleaning care before the surgery and early suspicion of the diagnosis.

Effects of Angiotensin Receptor Blockers on Streptozotocin-Induced Diabetic Cataracts.

This study aimed to determine the role of oxidative stress produced by the renin-angiotensin system (RAS) in cataract formation in streptozotocin-induced diabetic rats (STZ) using angiotensin II receptor blockers (ARBs). Rats were treated with streptozotocin and orally administered candesartan (2.5 mg/kg/day) or a normal diet for 10 weeks until sacrifice. Cataract progression was assessed through a slit-lamp examination. Animals were euthanized at 18 weeks, and the degree of cataract progression was evaluated. Oxidative stress was also assessed. In STZ-treated rats, lens opacity occurred at 12 weeks. Cataract progression was inhibited in the ARB-treated group compared with the placebo group (p < 0.05). STZ-treated rats exhibited upregulated angiotensin-converting enzyme (ACE) gene expression than control rats. Oxidative stress-related factors were upregulated in the placebo-treated group but suppressed in the ARB-treated group. A correlation coefficient test revealed a positive correlation between ACE gene expression and oxidative stress-related factors and a negative correlation between ACE and superoxide dismutase. Immunostaining revealed oxidative stress-related factors and advanced glycation end products in the lens cortex of the placebo-treated group. The mechanism of diabetic cataracts may be related to RAS, and the increase in focal ACE and angiotensin II in the lens promotes oxidative stress-related factor production.

Clinical applications of the chimeric anterolateral thigh (ALT) flap in head and neck reconstruction.

BACKGROUND: Surgical site infection (SSI) is a common complication following head and neck surgery. Dead space at the excision site can increase the risk of infection, abscess formation, and mortality. Herein, we evaluated the performance of the chimeric anterolateral thigh (ALT) flap in addressing these concerns. METHODS: Patients who underwent oncologic head and neck reconstruction between October 2016 and November 2021 were divided in two groups: a normal ALT flap and a chimeric dead space filling (DSF) ALT-vastus lateralis flap group. We evaluated the postoperative outcomes. RESULTS: Twenty-five patients treated with normal ALT flaps (34.7%) and 47 with DSF ALT flap group (65.2%) were included. Only one ALT per case was necessary. Most of the cases involved tongue (31.9%) and lower gingival reconstruction (27.8%). The time to harvest the DSF ALT flap was 134.3 min when compared to the normal ALT flap (116.2 min, p < .001). Vascular occlusion, flap loss, partial necrosis, and fat necrosis were not observed among the different groups. CONCLUSION: The DSF process can be used as a preventive measure for SSI or vessel exposure due to radiation-induced skin damage. This flap allows same-site reconstruction if the primary tumor recurs by using the pedicle of the chimeric flap for reattachment of another free flap.

Characteristics and Limitations of Video-capillaroscopy in Reconstructive Microsurgery for Different Histologic Components of Flaps.

Indocyanine green, ultrasonography, and handheld Doppler can be used to evaluate blood flow at the donor and recipient site during microvascular reconstruction. However, these methods do not provide direct visualization and assessment of real-time blood flow. Video-capillaroscopy has been shown to be useful in clinical practice to assess microcirculation in rheumatologic disorders. In this report we used video-capillaroscopy to assess different tissue components involved in microvascular surgery. Seven patients who underwent head and neck oncologic microvascular reconstruction between November 2021 and February 2022 were included in this study. Video-capillaroscopy (GOKO-BscanZD, GOKO Imaging Devices Co., Ltd., Japan) was used to evaluate the donor-site and recipient-site tissue components. Optimal red blood cell movement was graded with a score of four, while no flow was graded with a score of 0. Seven myocutaneous flaps and seven recipient sites were evaluated. For the donor-site, our analysis demonstrated a significantly higher video-capillaroscopy quality for skin (3.43), adipose tissue (3.7) and perforators (3.7) when compared with muscle (0.429), muscle fascia (0.857), and de-epithelialized skin (1) (P < 0.001). For the recipient-site, a significantly higher video-capillaroscopy quality for skin (2.7), adipose tissue (3.5), and the periosteum (2.1) was noted when compared with muscle (0) (P < 0.001). Video-capillaroscopy efficiency is limited in the muscular component and injured (de-epithelialized) skin surface areas of flaps. Herein, we provide evidence that assessment of flap perfusion with video-capillaroscopy can be reliably achieved in the skin, periosteum, perforators, and adipose tissue. Video-capillaroscopy is expected to be applied for intraoperative real-time blood flow evaluation.

Intraoperative Identification of Perforator Spasm and Decreased Pulsation Using Video-capillaroscopy during Free Flap Harvest.

Temporary or prolonged vascular spasm can be appreciated when perivascular dissection is performed for microvascular reconstruction. Due to a lack of reliable assessment modalities, the resolution of spasm at the periphery of perforators cannot be determined by naked eyes or surgical loupes. To address this conundrum, we aimed to observe the state of perforator vessel spasm after flap elevation using video-capillaroscopy. Between November 2021 and February 2022, seven free flaps were evaluated with video-capillaroscopy to determine the incidence of vasospasm in less than 1 mm-diameter perforators. The type of perforator spasm after flap elevation was divided into six types according to the video-capillaroscopy findings: type A, no spasm/decreased pulsation (S/DP); type B, S/DP with recovery within 5 minutes; type C, S/DP requiring papaverine hydrochloride spraying and hot water treatment (PHS+HWT) resulting in recovery within 5 minutes; type D, S/DP requiring PHS+HWT resulting in recovery within 10 minutes; type E, S/DP requiring PHS+HWT resulting in recovery within 15 minutes; and type F, S/DP with no recovery of pulsation even after PHS+HWT. Twenty-five perforators were evaluated, 3.57 perforators (range, 3-4) per flap. Using our classification for perforator vessel spasms on video-capillaroscopy, observations of five perforating branches were classified as type A, seven as type B, six as type C, five as type D, and two as type E. No type F spasm was observed. With video-capillaroscopy it is possible to confirm if blood flow deterioration occurs even in areas that are difficult to determine macroscopically. Video-capillaroscopy, a noninvasive imaging modality, is a useful alternative for the intraoperative evaluation of perforator flow and spasm.

Study protocol for periodontal tissue regeneration with a mixture of autologous adipose-derived stem cells and platelet rich plasma: A multicenter, randomized, open-label clinical trial.

Introduction: Adipose-derived stem cells (ASCs) secrete various growth factors to promote wound healing and to regenerate various tissues, such as bone, cartilage, and fat tissue. Subcutaneous adipose tissue is a considerable cell source in clinical practice and can be collected relatively easily and safely under local anesthesia. Moreover, platelet-rich plasma (PRP), a plasma component containing many platelets purified by centrifuging the collected blood, also promotes wound healing. PRP can be easily gelled and is therefore attracting attention as a scaffolding material for transplanted cells. The usefulness of a mixture of ASCs and PRP for periodontal tissue regeneration has been in vitro demonstrated in our previous study. The aim of this study is to present the protocol of translation of tissue regeneration with ASCs and PRP into practical use, evaluating its efficacy. Methods: This study is a multicenter, randomized, open-label comparative clinical trial. Fifteen patients will be randomly assigned to the treatment with mixture of ASCs and PRP or enamel matrix derivate administration into periodontal tissue defects. Increase in height of new alveolar bone in the transplanted area will be evaluated. The evaluation will be performed using dental radiographs after 36 weeks of transplantation. Occurrence of adverse events will be evaluated as secondary outcome. Results: This clinical study was initiated after meeting the regulations to be complied with, including ethical review and regulatory notifications. Conclusions: If effective, this cell therapy using autologous mesenchymal stem cells can represent a useful medical technology for regeneration of periodontal defects.

Fine mapping of Rf5 region for a sorghum fertility restorer gene and microsynteny analysis across grass species.

Cytoplasmic male sterility (CMS) is widely used to control pollination in the production of commercial F1 hybrid seed in sorghum. So far, 6 major fertility restorer genes, Rf1 to Rf6, have been reported in sorghum. Here, we fine-mapped the Rf5 locus on sorghum chromosome 5 using descendant populations of a 'Nakei MS-3A' × 'JN43' cross. The Rf5 locus was narrowed to a 140-kb region in BTx623 genome (161-kb in JN43) with 16 predicted genes, including 6 homologous to the rice fertility restorer Rf1 (PPR.1 to PPR.6). These 6 homologs have tandem pentatricopeptide repeat (PPR) motifs. Many Rf genes encode PPR proteins, which bind RNA transcripts and modulate gene expression at the RNA level. No PPR genes were detected at the Rf5 locus on the corresponding homologous chromosome of rice, foxtail millet, or maize, so this gene cluster may have originated by chromosome translocation and duplication after the divergence of sorghum from these species. Comparison of the sequences of these genes between fertile and CMS lines identified PPR.4 as the most plausible candidate gene for Rf5.

Combined ALT, Estlander, and Upper Lip Flap for Defects Involving the Oral Commissure.

Lip defects (including the corners of the mouth) are a reconstructive challenge in terms of both aesthetic and functional outcomes. When oral cancer resection results in defects that extend beyond the corners of the mouth to the buccal mucosa and buccal skin, it is difficult to perform reconstructive surgery using only a local flap, and a free flap must be used in combination. In this report, we present a case of reconstructive surgery of the corners of the mouth, buccal mucosa, and buccal skin after tumor resection for buccal mucosal squamous cell carcinoma in a 70-year-old man. The patient presented with a change in an oral mucosal ulcer for a period of 1 year. After biopsy of the ulcerated area, he was pathologically diagnosed with squamous cell carcinoma. After tumor resection, including the corners of the mouth, lips, and cheek skin, and neck dissection, the patient underwent reconstructive surgery using an extended upper lip flap combined with an Estlander flap and a free anterolateral thigh flap. Two months after surgery, the patient was able to consume regular food. At 24 months of follow-up, the patient was able to speak normally without any restrictive symptoms such as fluid leakage from the corner of the mouth. Lip sensation restoration was optimal. This method using the combination of an anterolateral thigh flap and extended Estlander flap is a markedly useful option for reconstructive surgery of defects around the corner of the mouth caused by wide excision of invasive cancer.

Effect of MNCQQ Cells on Migration of Human Dermal Fibroblast in Diabetic Condition.

A major symptom of diabetes mellitus (DM) is unfit hyperglycemia, which leads to impaired wound healing. It has been reported that the migration of fibroblasts can be suppressed under high glucose (HG) conditions. In our previous study, we introduced a serum-free culture method for mononuclear cells (MNCs) called quantity and quality control culture (QQc), which could improve the vasculogenic and tissue regeneration ability of MNCs. In this study, we described a culture model in which we applied a high glucose condition in human dermal fibroblasts to simulate the hyperglycemia condition in diabetic patients. MNC-QQ cells were cocultured with fibroblasts in this model to evaluate its role in improving fibroblasts dysfunction induced by HG and investigate its molecular mechanism. It was proven in this study that the impaired migration of fibroblasts induced by high glucose could be remarkably enhanced by coculture with MNC-QQ cells. PDGF B is known to play important roles in fibroblasts migration. Quantitative PCR revealed that MNC-QQ cells enhanced the gene expressions of PDGF B in fibroblasts under HG. Taken with these results, our data suggested a possibility that MNC-QQ cells accelerate wound healing via improving the fibroblasts migration and promote the gene expressions of PDGF B under diabetic conditions.

Real-Time Assessment of Free Flap Capillary Circulation Using Videocapillaroscopy.

BACKGROUND: Free tissue transfer is a common method of reconstruction for various surgical defects. Many clinical assessment methods, including flap color monitoring and capillary refill time measurements, are commonly used to assess the microcirculation of the flap, yet there is no objective tool available that can clear real-time visualization of the flap microcirculation. The purpose of this study was to use a novel videocapillaroscope to evaluate the circulation changes on free flap skin surfaces while purposely clamping pedicle vessels. METHODS: Ten patients who underwent free flap transfer for head and neck cancer from November of 2019 to June of 2020 were included in the study. Videocapillaroscopic observation was performed after flap elevation, and changes in the flap skin capillary circulation with artery-controlled and vein-controlled clamping were recorded. RESULTS: Average total surgery time was 517.91 minutes (SD, 73.3 minutes), average flap elevation time was 102.9 minutes (SD, 18.3 minutes). When the pedicle artery or vein was purposely clamped, the movement of red blood cells in blood vessels stopped; when clamps were removed after 60 seconds, the restoration of red blood cell movements was rapidly observed. When the pedicle artery was clamped, the number of visualizable blood vessels decreased and flap color became relatively white. When the pedicle vein was clamped, the number of visualizable blood vessels increased, and flap color tone had a tendency toward red. CONCLUSION: Novel videocapillaroscopy can be utilized for objective real-time flap monitoring by directly visualizing flap skin capillary microcirculation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Dental Silicone-based Surgical Guides to Harvest the Chimeric Scapular Flap: Preventing Iatrogenic Vascular Injury.

The angular branch of the thoracodorsal artery and the periosteal branches of the circumflex scapular artery can be easily injured while harvesting a chimeric scapular flap. Thus, we reported the use of 3D printed scapular models using CT angiography to prepare inexpensive surgical guides from autoclavable dental silicone impressions for scapular flap harvest. Mandibular and scapular models were prepared using a 3D printer for 11 patients undergoing chimeric scapular flap transfer following mandibular resection. During preoperative simulation surgery, we molded dental silicone accordingly with scapular models to produce surgical cutting guides. Six men (54.5%) and five women (45.5%) were included. The average age of patients was 65.4 years. Fourteen bone units were reconstructed as three patients needed two bone segments (27.3%) whereas eight patients required reconstruction of one bone segment (72.7%). The mean flap harvest time and total surgical time were 52.1 min and 633.8 min, respectively. The mean duration for osteotomies and bone plate fixation was 26.2 min. The difference between the length of the preoperative surgical model (64.92 mm) and the postoperative 3D-CT measurements (64.48 mm) was not statistically significant (0.95 mm, P = 0.397). No injuries were caused to the angular and periosteal vessels. Four patients exhibited donor-site seroma (36.4%). The cost of the dental silicone for surgical guide was only $5 per patient. Dental silicone-based surgical guides help minimize the risk of vascular injury while harvesting chimeric scapular flaps. The osteotomies were performed with precision and in a time-efficient manner.

Dynamic Changes on Video-capillaroscopy and Potential Microsurgical Application: Temperature and Skin Surface Readings.

Video-capillaroscopy is being explored as a potential tool for microsurgical flap monitoring. A detailed examination of the effect of temperature on capillary changes using video-capillaroscopy is yet to be investigated. We analyzed the video-capillaroscopy findings on different skin areas often used for flap harvest at normal body temperatures and at lower temperatures. Skin capillaries at the lateral thigh, anterior forearm, mid-axillary line, abdomen, and fingertips were observed using video-capillaroscopy in 20 healthy Japanese individuals. Further, ImageJ software was used to measure the blood vessel area and blood flow velocity, and comparisons were drawn between normal body temperature and lower body temperature states. All measures of blood vessel area and average blood flow velocity for the different anatomical regions were significantly different before and after cooling (P < 0.001). The mean reduction rate of the vessel area was significantly different among anatomic regions (P < 0.001). Post-hoc analysis revealed a significant difference in the vessel area reduction rate between anatomic areas (P < 0.05); except when comparing the thigh versus finger, the forearm versus abdomen, and the mid-axillary line versus abdomen. The mean blood flow velocity was significantly different among anatomic regions (P < 0.001). Post-hoc analysis revealed a significant difference between the thigh and forearm (P = 0.009), the forearm and fingertip (P = 0.001), and the abdomen and fingertip (P = 0.004). Decreasing the skin temperature resulted in a significant vasoconstriction and reduction in capillary flow velocity. It is imperative to keep the monitored area warm during video-capillaroscopy assessment to avoid false diagnosis of vascular occlusion.

Phase I/IIa Feasibility Trial of Autologous Quality- and Quantity-Cultured Peripheral Blood Mononuclear Cell Therapy for Non-Healing Extremity Ulcers.

Non-healing wounds are among the main causes of morbidity and mortality. We recently described a novel, serum-free ex vivo expansion system, the quantity and quality culture system (QQc), which uses peripheral blood mononuclear cells (PBMNCs) for effective and noninvasive regeneration of tissue and vasculature in murine and porcine models. In this prospective clinical study, we investigated the safety and efficacy of QQ-cultured peripheral blood mononuclear cell (MNC-QQ) therapy for chronic non-healing ischemic extremity wounds. Peripheral blood was collected from 9 patients with 10 chronic (>1 month) non-healing wounds (8 males, 1 female; 64-74 years) corresponding to ischemic extremity ulcers. PBMNCs were isolated and cultured using QQc. Within a 20-cm area surrounding the ulcer, 2 × 107 cells were injected under local anesthesia. Wound healing was monitored photometrically every 2 weeks. The primary endpoint was safety, whereas the secondary endpoint was efficacy at 12-week post-injection. All patients remained ambulant, and no deaths, other serious adverse events, or major amputations were observed for 12 weeks after cell transplantation. Six of the 10 cases showed complete wound closure with an average wound closure rate of 73.2% ± 40.1% at 12 weeks. MNC-QQ therapy increased vascular perfusion, skin perfusion pressure, and decreased pain intensity in all patients. These results indicate the feasibility and safety of MNC-QQ therapy in patients with chronic non-healing ischemic extremity wounds. As the therapy involves transplanting highly vasculogenic cells obtained from a small blood sample, it may be an effective and highly vasculogenic strategy for limb salvage.

Three cases of macular hole that occurred in inferior scleral staphyloma associated with tilted disc syndrome: a case series.

BACKGROUND: The objective is to examine the clinical characteristics of three patients with macular hole that occurred in inferior posterior staphyloma associated with tilted disc syndrome. CASE PRESENTATIONS: This study involved three eyes of three Japanese female patients (mean age 76.0 years, range 73-84 years) with macular hole occurring in inferior posterior staphyloma associated with tilted disc syndrome. One of the three eyes was slightly myopic, while the other two eyes were highly myopic. In all three eyes, the macular hole was found to be located in or near the margin of the inferior posterior staphyloma. In one eye, the extent of retinoschisis was rather broad in the margin of the macular hole, and another eye had a history of treatment for choroidal neovascularization. As surgical treatment, the internal limiting membrane in areas surrounding the macular hole was detached after producing artificial posterior vitreous detachment, and a gas tamponade was performed. It was found during surgery that the extensibility of the retina in the margin of the MH was decreased in the three eyes as compared with a usual macular hole. Although the macular hole was successfully closed in all three cases post surgery, the layer structure of the central retina was poorly repaired in all three cases and choroidal neovascularization remained in one case. In all three cases, corrected visual acuity remained at 0.3-0.5 post surgery. CONCLUSIONS: Our findings showed poor improvement of visual acuity in all three cases post surgery, even if closure of the macular hole is achieved, thus suggesting that in cases of macular hole associated with tilted disc syndrome and inferior posterior staphyloma, the presence of macular dysfunction existing prior to the onset of macular hole affects visual prognosis.

Use of Dental Impression Silicone to Fabricate Simple Surgical Guides in Mandibular Reconstruction∗.

BACKGROUND: Several recent reports have described the development and use of three-dimensional (3D) printed surgical osteotomy guides. However, these methods: are usually costly. Here, we introduce a novel method of manufacturing surgical guides built from inexpensive, easy-to-use, and sterilizable dental impression silicone. METHODS: Mandibular and fibular models were prepared using a 3D printer for 10 patients undergoing free fibula flap transfer after mandibular resection. During preoperative simulation surgery, Protesil labor, a dental silicone, was molded to the same size as the fibular models to act as surgical guides. RESULTS: The authors compared pre- and post-operative bone angles and bone lengths for all cases using simulation surgery models and postoperative 3D computed tomography. Mean bone angle difference was 2.6° and mean bone length difference was 1.7 mm. Cost of the dental silicone was approximately US$5/patient. CONCLUSIONS: In our series this method allowed the surgeon to perform an accurate osteotomy, inexpensively and time-efficiently.

MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds.

INTRODUCTION: Intractable ulcers may ultimately lead to amputation. To promote wound healing, researchers developed a serum-free ex vivo peripheral blood mononuclear cell quality and quantity culture (MNC-QQc) as a source for cell therapy. In mice, pigs, and even humans, cell therapy with MNC-QQc reportedly yields a high regenerative efficacy. However, the mechanism of wound healing by MNC-QQc cells remains largely unknown. Hence, using an in vitro wound healing model, this study aimed to investigate MNC-QQc cells and the migratory potential of dermal fibroblasts. METHODS: After separation from a 50 mL blood sample from healthy individuals, mononuclear cells were cultured for 7 days in a serum-free ex vivo expansion system with five different cytokines (MNC-QQc method). The effects of MNC-QQc cells on human dermal fibroblast migration were observed by scratch assay. An angiogenesis array screened the MNC-QQc cell supernatant for proteins related to wound healing. Finally, fibroblast migration was confirmed by observing the intracellular signal transduction pathways via Western blot. RESULTS: The migration of fibroblasts co-cultured with MNC-QQc cells increased by matrix metallopeptidase-9 (MMP9) secretion, as suggested by the angiogenesis array. Furthermore, the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in fibroblast/MNC-QQc cell co-culture and fibroblast culture with added recombinant human MMP9 protein increased. When fibroblasts were cultured with either an MMP9 inhibitor or a STAT3 inhibitor, both fibroblast migration and STAT3 phosphorylation were significantly suppressed. CONCLUSIONS: MNC-QQc cells promote wound healing by the secretion of MMP9, which induces fibroblast migration via the STAT3 signaling pathway.