Exclusive expression of KANK4 promotes myofibroblast mobility in keloid tissues.

Keloids are characterized by abnormal wound healing with excessive accumulation of extracellular matrix. Myofibroblasts are the primary contributor to extracellular matrix secretion, playing an essential role in the wound healing process. However, the differences between myofibroblasts involved in keloid formation and normal wound healing remain unclear. To identify the specific characteristics of keloid myofibroblasts, we initially assessed the expression levels of well-established myofibroblast markers, α-smooth muscle actin (α-SMA) and transgelin (TAGLN), in scar and keloid tissues (n = 63 and 51, respectively). Although myofibroblasts were present in significant quantities in keloids and immature scars, they were absent in mature scars. Next, we conducted RNA sequencing using myofibroblast-rich areas from keloids and immature scars to investigate the difference in RNA expression profiles among myofibroblasts. Among significantly upregulated 112 genes, KN motif and ankyrin repeat domains 4 (KANK4) was identified as a specifically upregulated gene in keloids. Immunohistochemical analysis showed that KANK4 protein was expressed in myofibroblasts in keloid tissues; however, it was not expressed in any myofibroblasts in immature scar tissues. Overexpression of KANK4 enhanced cell mobility in keloid myofibroblasts. Our results suggest that the KANK4-mediated increase in myofibroblast mobility contributes to keloid pathogenesis.

＜Editors' Choice＞ Supernatant from activated omentum accelerates wound healing in diabetic mice wound model.

Diabetic wounds are considered one of the most frequent and severe complications of diabetes mellitus. Recently, the omentum has been used in diabetic wound healing because of its tissue repair properties. The activated omentum is richer in growth factors than the inactivated, thereby contributing to the wound healing process. To further investigate the effect of activated omentum conditioned medium (aOCM) on diabetic wound healing, we injected supernatant from aOCM, saline-OCM (sOCM), inactivated-OCM (iOCM), and medium (M) subcutaneously upon creation of a cutaneous wound healing model in diabetic mice. Wound area (%) was evaluated on days 0, 3, 5, 7, 9, 11, 14, 21, and 28 post-operation. At 9 and 28 d post-operation, skin tissue was harvested and assessed for gross observation, neovascularization, peripheral nerve fiber regeneration, and collagen deposition. We observed that aOCM enhanced the wound repair process, with significant acceleration of epidermal and collagen deposition in the surgical lesion on day 9. Additionally, aOCM displayed marked efficiency in neovascularization and peripheral nerve regeneration during wound healing. Thus, aOCM administration exerts a positive influence on the diabetic mouse model, which can be employed as a new therapy for diabetic wounds.

＜Editors' Choice＞ Long-term outcomes of lateral skull base reconstruction with a free omental flap and facial nerve reconstruction.

In lateral skull base reconstruction, it is necessary to seal the defect in the lateral skull base, fill the dead space, and, sometimes, reconstruct the facial nerve. However, this procedure is difficult to perform with a standard musculocutaneous flap. Therefore, for such cases, an omental flap is used in our hospital because of its flexibility. In this study, we report our experience with the procedure (lateral skull base reconstruction with a free omental flap) and its long-term outcome and facial nerve reconstruction, with special focus on facial nerve recovery. This study is a technical note and a retrospective review. It was conducted in Nagoya University Hospital. Overall, 16 patients (12 women and 4 men; mean age: 55.1 years) underwent lateral skull base reconstruction with a free omental flap after subtotal temporal bone resection or lateral temporal bone resection during 2005-2017. The main outcome measures were postoperative complications and facial nerve recovery: Yanagihara score and House-Brackmann grading system. Complications included partial necrosis and minor cerebrospinal fluid leakage in 2 patients. Facial nerve recovery could be observed more than 12 months after surgery, with a mean Yanagihara score of 19.6 and House-Brackmann grade of 3.60. The free omental flap is a reliable method for lateral skull base reconstruction, especially in cases where facial nerve reconstruction is needed. To the best of our knowledge, this is the first report on facial nerve recovery after lateral skull base reconstruction.

Hydroxyapatite-coated titanium oxide ameliorates dextran sulphate sodium-induced colitis by attenuating both innate and acquired immune reaction.

Introduction: Titanium oxide (TiO2) is a widely used oxidizer for environmental management. The power of TiO2 has been demonstrated by its photocatalytic activity. Hydroxyapatite (HA)-coated TiO2 (HA-TiO2) was used to test the in vivo effect on dextran sulphate sodium (DSS)-induced colitis in mice. Material and methods: Mice were monitored for body weight and then sacrificed on the seventh day, and the colon length was measured. Their faeces were analysed for intestinal microbiota distribution, and colon tissue was subjected to histological examination and immunohistochemical analysis. Results: Weight loss was significantly lower in HA-TiO2-fed mice than in mice without HA-TiO2. The colon length in the DSS colitis-induced mice was shortened, but HA-TiO2 feeding lessened this effect. Histological and immunohistochemical analyses of the colon revealed that macrophages and CD4+CD8+ T cells were observed in the colitis-occurring site, indicating the involvement of innate and acquired immunity in determining the degree of DSS-induced colitis. Intestinal microbiota analysis in faeces revealed changes in the distribution of multiple bacterial species after DSS colitis induction, and the increase/decrease of 2 Clostridium (sub)clusters moved in response to the colitis phenomenon. All the described effects of HA-TiO2 were photocatalytic activity-dependent because mice that were kept in the dark showed similar results to those treated with DSS alone without HA-TiO2. Conclusions: HA-coated TiO2 ameliorated DSS-induced colitis through photocatalytic activity, while HA-TiO2 diminished the changes in intestinal microbiota and immune reactions caused by DSS.

Artificial PGA/Collagen-based Bilayer Conduit in Short Gap Interposition Setting Provides Comparable Regenerative Potential to Direct Suture.

The aim of this study was to evaluate whether the Nerbridge, an artificial polyglycolic acid conduit with collagen matrix, is comparable to direct nerve suture in a rat sciatic nerve injury model in a short-gap interposition (SGI) setting. Methods: Sixty-six female Lewis rats were randomly divided into the sham group (n = 13); no reconstruction (no-recon) group (n = 13; rat model with 10 mm sciatic nerve defect); direct group (n = 20; rat sciatic nerve injury directly connected by 10-0 Nylon); and SGI group (n = 20; sciatic nerve injury repaired using 5-mm Nerbridge). Motor function and histological recovery were evaluated. The sciatic nerve and gastrocnemius muscle were harvested for quantification of the degree of nerve regeneration and muscle atrophy. Results: The SGI and direct groups achieved equal recovery in both functional and histological outcomes. At weeks 3 and 8 postsurgery, there was a significant improvement in the sciatic functional index of the SGI group when compared with that of the no-recon group (P < 0.05). Furthermore, the direct and SGI groups had less muscle atrophy at 4 and 8 weeks postsurgery compared with the no-recon group (P < 0.05). The axon density and diameter at the distal site in the SGI group were significantly higher than that in the no-recon group and comparable to that in the direct and sham groups. Conclusion: An artificial nerve conduit has equal potential as direct suture in motor nerve reconstruction when used in the SGI setting.

Surgical Strategy for Squamous Cell Carcinoma of the External Auditory Canal: Management of Locally Advanced Cases with Skull Base Involvement.

Objective Surgical indications for advanced-stage squamous cell carcinoma (SCC) of the external auditory canal (EAC) are highly dependent on the skull base surgery team. The aim of this study was to evaluate the surgical outcomes in patients with SCC of the EAC and to clarify the surgical indication of far advanced cases using the T4 subclassification. Methods Patients with SCC of the EAC who underwent curative treatment from 2002 to 2021 at our hospital were retrospectively reviewed. Clinical and surgical results, including operative data, overall survival (OS), and disease-specific survival (DSS), were analyzed. To clarify the surgical indication for advanced-stage tumors, we proposed the T4 subclassification. Results In the 46 patients included in the study, 8 patients had T1 tumors, 10 had T2 tumor, 5 had T3 tumors, and 23 had T4 tumors. The 5-year DSS with T1, T2, T3, and T4 tumors were 100, 85.7, 100, and 61.7%, respectively. No prognostic impacts for margin status were found between the 5-year OS and DSS ( p = 0.23 and 0.13, respectively). Patients with far-advanced-stage (T4b) tumors were significantly associated with shorter DSS than those with early-stage (T1/T2) and advanced-stage (T3/T4a) tumors ( p = 0.007 and 0.03, respectively). Conclusion The present study focused on patients with SCC of the EAC at a university hospital over a period of 20 years, especially with skull base involvement, and a T4 subclassification was proposed. Complete tumor resection in an en bloc fashion could help achieve a good survival rate even in patients with locally advanced tumors.

Feasibility and Safety of Microvascular Anastomoses Within Previously-Dissected Neck Regions.

The selection of appropriate recipient vessels is important for the success of head and neck reconstruction. Vessels located outside of previously-dissected neck regions tend to be more frequently selected due to relative ease of preparation. However, some advantages are offered regarding dead space filling and formation by using vascular anastomoses within regions previously dissected, or reusing former free flap pedicle due to their proximity to the defect. We analyzed microsurgical anastomoses in patients requiring oral reconstruction who had previously undergone neck dissection. Contralateral vascular anastomoses were preoperatively planned in 10 cases of which 9 could be successfully performed (achievement rate, 90%). Ipsilateral side anastomoses were planned in 28 cases, with 26 anastomosed as planned (achievement rate, 92.9%). There was no statistically significant difference between the two groups. Vascular anastomosis within the scar region can be performed safely, based on preoperative planning and intraoperative judgment.

Upper thoracic empyema and concomitant superior vena cava syndrome treated with reconstructive surgery using a pedicled omental flap.

Superior vena cava (SVC) syndrome refers to a constellation of symptoms secondary to obstruction of blood flow through the SVC. In this condition, venous blood that usually drains into the SVC is diverted into the inferior vena cava (IVC) via collateral veins. Reconstructive surgery is challenging in such cases owing to the anomalous venous system. In this case report, we describe reconstructive surgery using a pedicled omental flap in a patient with upper thoracic empyema and concomitant SVC syndrome. A 68-year-old man underwent resection of malignant thymoma, the bilateral brachiocephalic veins, and a part of the right upper lobe, followed by polytetrafluoroethylene (PTFE) graft placement for venous system reconstruction, 2 years prior to presentation. He developed postoperative upper thoracic cavity empyema, which necessitated PTFE graft removal. Although the infection was controlled after 2 months, multiple right upper lobe pulmonary fistulas persisted, and the patient was referred to our department for further evaluation. Contrast-enhanced computed tomography revealed SVC syndrome characterized by SVC obstruction and consequent drainage of venous blood from the upper trunk into the IVC via collateral vessels. We debrided necrotic and infected tissues, and a pedicled omental flap was placed for upper lobe fistula coverage. The patient showed an uncomplicated postoperative course, and no recurrent empyema or pulmonary fistulas were observed 3 years postoperatively. Flaps associated with the SVC system show high venous pressures. The use of a pedicled omental flap was deemed feasible because this graft reaches the upper thorax even though it is associated with the IVC system.

Development of a Novel Scar Screening System with Machine Learning.

BACKGROUND: Hypertrophic scars and keloids tend to cause serious functional and cosmetic impediments to patients. As these scars are not life threatening, many patients do not seek proper treatment. Thus, educating physicians and patients regarding these scars is important. The authors aimed to develop an algorithm for a scar screening system and compare the accuracy of the system with that of physicians. This algorithm was designed to involve health care providers and patients. METHODS: Digital images were obtained from Google Images (Google LLC, Mountain View, Calif.), open access repositories, and patients in the authors' hospital. After preprocessing, 3768 images were uploaded to the Google Cloud AutoML Vision platform and labeled with one of the four diagnoses: immature scars, mature scars, hypertrophic scars, and keloid. A consensus label for each image was compared with the label provided by physicians. RESULTS: For all diagnoses, the average precision (positive predictive value) of the algorithm was 80.7 percent, the average recall (sensitivity) was 71 percent, and the area under the curve was 0.846. The algorithm afforded 77 correct diagnoses with an accuracy of 77 percent. Conversely, the average physician accuracy was 68.7 percent. The Cohen kappa coefficient of the algorithm was 0.69, while that of the physicians was 0.59. CONCLUSIONS: The authors developed a computer vision algorithm that can diagnose four scar types using automated machine learning. Future iterations of this algorithm, with more comprehensive accuracy, can be embedded in telehealth and digital imaging platforms used by patients and primary doctors. The scar screening system with machine learning may be a valuable support tool for physicians and patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Influence of background characteristics in responders of regenerative therapy by periurethral injection of adipose-derived regenerative cells for male stress urinary incontinence.

OBJECTIVES: To determine if the male responders with post-prostatectomy incontinence in the ADRESU study, which is a clinical trial of regenerative therapy by periurethral injection of adipose-derived regenerative cells, are influenced by any background characteristics. METHODS: Briefly, autologous adipose-derived regenerative cells isolated from abdominal adipose tissue and a mixture of adipose-derived regenerative cells with fat tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Sixteen out of 43 patients (37.2%) responded to treatment (responders) and exhibited improvement in the urine leakage volume, defined as >50% reduction from baseline determined by the 24-hour pad test at 52 weeks of treatment (or last visit within 52 weeks). Background data such as age, body weight, method of prostatectomy, baseline frequency of leaks, number of leaks, number of pad changes, International Consultation on Incontinence Questionnaire-Short Form, King's Health Questionnaire, urodynamic urethral function including functional profile length and maximum urethral closure pressure, and abdominal leak point pressure were collected and compared between responders and nonresponders. RESULTS: None of the background factors influenced improvement in the responders as compared with the nonresponders. However, a significant between-group difference in the rates of decrease in urine leakage volume was noted in patients of younger age (<70 years), compared with those of older age (≥70 years) from 2 to 26 weeks of treatment. CONCLUSION: A greater decrease in urine leakage volume was noted in the younger patient group than in the older patient group.

Combined Vascular Resection for Locally Advanced Perihilar Cholangiocarcinoma.

OBJECTIVE: To evaluate the efficacy and safety of combined vascular resection (VR) in advanced perihilar cholangiocarcinoma (PHC). SUMMARY OF BACKGROUND DATA: Hepatectomy combined with portal vein resection (PVR) and/or hepatic artery resection (HAR) is technically demanding but an option only for tumor eradication against PHC involving the hilar hepatic inflow vessels; however, its efficacy and safety have not been well evaluated. METHODS: Patients diagnosed with PHC during 2001-2018 were included. Patients who underwent resection were divided according to combined VR. Patients undergoing VR were subdivided according to type of VR. Postoperative outcomes and OS were compared between patient groups. RESULTS: Among the 1055 consecutive patients, 787 (75%) underwent resection (without VR: n = 484, PVR: n = 157, HAR: n = 146). The incidences of postoperative complications and mortality were 49% (without VR vs with VR, 48% vs 50%; P= 0.715) and 2.1% (without VR vs with VR, 1.2% vs 3.6%; P= 0.040), respectively. The OS of patients who underwent resection with VR (median, 30 months) was shorter than that of those who underwent resection without VR (median, 61 months; P < 0.0001); however, it was longer than that of those who did not undergo resection (median, 10 months; P < 0.0001). OS was not significantly different between those who underwent PVR and those who underwent HAR (median, 29 months vs 34 months; P = 0.517). CONCLUSION: VR salvages a large number of patients from having locally advanced PHC that is otherwise unresectable and is recommended if the hilar hepatic inflow vessels are reconstructable, providing acceptable surgical outcomes and substantial survival benefits.

Peripheral Nerve Regeneration Using Different Germ Layer-Derived Adult Stem Cells in the Past Decade.

Peripheral nerve injuries (PNIs) are some of the most common types of traumatic lesions affecting the nervous system. Although the peripheral nervous system has a higher regenerative ability than the central nervous system, delayed treatment is associated with disturbances in both distal sensory and functional abilities. Over the past decades, adult stem cell-based therapies for peripheral nerve injuries have drawn attention from researchers. This is because various stem cells can promote regeneration after peripheral nerve injuries by differentiating into neural-line cells, secreting various neurotrophic factors, and regulating the activity of in situ Schwann cells (SCs). This article reviewed research from the past 10 years on the role of stem cells in the repair of PNIs. We concluded that adult stem cell-based therapies promote the regeneration of PNI in various ways.

A Novel Technique to Lengthen the Reverse Latissimus Dorsi Muscle Flap Arc.

Reconstruction of the lower lumbar region is challenging for surgeons due to limited locoregional flap choices. The latissimus dorsi muscle flap is a mainstay for this area; however, there are several limitations, including that the dominant thoracodorsal artery and vein pedicle-based flaps are not reachable for reconstruction of the lumbar region, while perforator of intercostal artery and veins pedicle-based reverse latissimus dorsi (RLD) flap mobility is limited by including multiple perforators. Here, we describe a novel operative technique that lengthens the rotation arc of RLD muscle flaps. The surgical technique is as follows: RLD is elevated based on lower perforator of intercostal artery and veins (usually including two of the eighth-11th perforators); thoracodorsal artery and vein are ligated; and the flap is mobilized toward the defect. When RLD was not reachable to the defect, the far aspect of the intercostal artery and vein from the defect was ligated and the perforator was elevated with the near aspect of the intercostal artery and vein from intercostal space. Because the intercostal space measured between approximately 3 cm and 4 cm, this dissection gained 3-4 cm of rotational arc per intercostal space. Moreover, because the lower ribs follow a medio-cranial to latero-caudal direction, this dissection enabled the flap to extend latero-caudally or medio-cranially while maintaining its blood supply. Other applications using this technique may involve expanding the RLD flap arc caudally, ventrally, and ipsilaterally. We believe this new technique provides a reliable alternative for lower back reconstruction.

Skull Base Invasion Patterns of Malignant Head and Neck Tumors: A Neurosurgical Perspective.

Objective Craniofacial resection (CFR) and temporal bone resection (TBR) on malignant head and neck tumors (MHNTs) invading skull base require accurate and precise determination of the tumor invasion. We investigated tumor skull base invasion patterns and surgical results in CFR and TBR cases. Methods We performed either CFR or TBR for 75 selected patients with the possibility of en bloc resection over the period between 2011 and 2018. The medical charts of the selected patients were reviewed. Results Primary tumor onset site (TOS) groups were: (1) nasal cavity/ethmoid sinus, 20 cases; (2) orbit, 10 cases; (3) maxillary sinus, 28 cases; and (4) external ear/temporomandibular joint, 17 cases. Grades for tumor invasion depth (TID) included: (I) extracranial invasion and skull base bone invasion; (II) extradural invasion; or (III) intradural invasion. Patients in groups 1 and 2 had a significantly higher frequency of grade II and III invasions than patients in groups 3 and 4. The main invasion site was nasal cavity superior wall and ethmoid sinus superior wall for group 1 tumors, orbit superior wall, and lateral skull base sphenoid bone for group 2 and 3 tumors, and lateral skull base temporal bone for group 4 tumors. Positive resection margins represented a significant negative prognostic factor. TID and TOS did not affect skull base margin status. Conclusion Skull base invasion of MHNTs exhibits certain fixed patterns in sites susceptible to invasion based on the TOS. The frequencies of extradural and intradural invasions differed, indicating the importance for accurate preoperative tumor evaluation.

Surgical Classification of Radical Temporal Bone Resection and Transcranial Tympanotomy: A Retrospective Study from the Neurosurgical Perspective.

OBJECTIVE: To review the authors' surgical experience with radical temporal bone resection (TBR) with an emphasis on the classification of skull base osteotomy and transcranial tympanotomy (TCT) that is required for middle ear transection. METHODS: We reviewed the records of 25 patients who underwent radical TBR at our facilities between 2011 and 2020. RESULTS: The osteotomy line of radical TBR was divided into 3 segments: anterior (A), medial (M), and posterior (P). Each segment was further classified as follows: A1, through the glenoid fossa (1 patient); A2, in front of the glenoid fossa (23 patients); A3, through the greater wing of the sphenoid bone (1 patient); M1, through the middle ear (16 patients); M2, through the inner ear (9 patients); P1, through the mastoid (9 patients); and P2, through the posterior cranial fossa (16 patients). The M segment was significantly associated with operation time and intraoperative blood loss. In all patients with M1 osteotomy, TCT was performed; TCT was classified into superior and far posterior approaches. A superior approach was performed in all 16 patients, whereas the far posterior approach was performed in only 7 patients with both M1 and P2 osteotomy. CONCLUSIONS: Our newly proposed osteotomy classification of radical TBR is suitable for minute but clinically important adjustment of the osteotomy line. TCT is an indispensable technique for M1 osteotomy; our newly proposed classification expands our understanding of TCT and how to incorporate this technique into radical TBR.

Biological characterization of adipose-derived regenerative cells used for the treatment of stress urinary incontinence.

OBJECTIVE: To assess the characteristics of adipose-derived regenerative cells, and provide supportive data explaining the mechanism of efficacy observed for the use of these cells in the treatment of stress urinary incontinence. METHODS: Adipose tissues were harvested by abdominal liposuction from healthy donors and patients with stress urinary incontinence. Adipose-derived regenerative cells were isolated from tissues using the Celution system, and assessed for their characteristics and ability to differentiate into smooth muscle cells. RESULTS: Adipose-derived regenerative cells isolated by the Celution system developed into fibroblastic colonies. Flow cytometric analysis of adipose-derived stem cell markers showed that adipose-derived regenerative cells were positive for CD34 and CD44, and negative for CD31. Immunofluorescence staining after differentiation showed that colony-forming cells were positive for alpha-smooth muscle actin, calponin and desmin, which are smooth muscle cell markers. A cytokine release assay showed that adherent cells secreted cytokines associated with angiogenesis, including vascular endothelial growth factor-A, angiopoietin-2 and placental growth factor. CONCLUSIONS: Adipose-derived regenerative cells collected by the Celution system might have clonogenic capacity and an angiogenetic function. These properties might contribute to the mechanisms through which regenerative cell therapy by periurethral injection of autologous adipose-derived regenerative cells ameliorates stress urinary incontinence.

Prospective Evaluation of Health-Related Quality of Life in Patients Undergoing Anterolateral Craniofacial Resection with Orbital Exenteration.

Objective This study was aimed to evaluate health-related quality of life in patients undergoing anterolateral craniofacial resection (AL-CFR) with orbital exenteration (OE) for malignant skull base tumors and to investigate the effects of early psychiatric intervention. Design Present study is a prospective, observational study. Setting The study took place at the hospital department. Participants Twenty-six consecutive patients were selected who underwent AL-CFR with OE at our hospital between 2005 and 2015. Main Outcome Measures Health-related quality of life was assessed preoperatively and 3, 6, 12, and 24 months after surgery using the Hospital Anxiety and Depression Scale (HADS) and medical outcomes study 8-items Short Form health survey (SF-8). In all cases, psychiatric intervention was organized by the consultation liaison psychiatry team preoperatively and postoperatively. Results Ten (38.0%) of the 26 patients died and 16 (62.0%) were alive and disease-free at the end of the study. The 3-year overall and disease-free survival rates were 64.9% and 53.3%, respectively. Twenty-one patients (80.8%) developed psychiatric complications after surgery and needed treatment with psychotropic medication. Before surgery, 28% of patients had HADS scores ≥8 for anxiety and 20% had scores ≥8 for depression. Seven of the eight items in the SF-8 were significantly lower than those for the general Japanese population. However, scores for all the SF-8 items gradually improved during postoperative follow-up, reaching approximately 50 points, which is the national standard value, at 2 years after surgery. Conclusions Craniofacial resection with OE was feasible and well tolerated in patients with malignant skull base tumors who received early psychiatric intervention to decrease the considerable psychological impact of this procedure.

Therapeutic angiogenesis using autologous adipose-derived regenerative cells in patients with critical limb ischaemia in Japan: a clinical pilot study.

Adipose-derived regenerative cell (ADRC) is a promising alternative source of autologous somatic stem cells for the repair of damaged tissue. This study aimed to assess the safety and feasibility of autologous ADRC implantation for therapeutic angiogenesis in patients with critical limb ischaemia (CLI). A clinical pilot study-Therapeutic Angiogenesis by Cell Transplantation using ADRCs (TACT-ADRC) study-was initiated in Japan. Adipose tissue was obtained by ordinary liposuction method. Isolated ADRCs were injected into the ischaemic limb. We performed TACT-ADRC procedure in five patients with CLI. At 6 months, no adverse events related to the TACT-ADRC were observed. No patients required major limb amputation, and ischaemic ulcers were partly or completely healed during the 6-month follow-up. In all cases, significant clinical improvements were seen in terms of rest pain and 6-min walking distance. Numbers of circulating CD34+ and CD133+ cells markers of progenitor cell persistently increased after ADRC implantation. The ratio of VEGF-A165b (an anti-angiogenic isoform of VEGF) to total VEGF-A in plasma significantly decreased after ADRC implantation. In vitro experiments, cultured with ADRC-conditioned media (CM) resulted in increased total VEGF-A and decreased VEGF-A165b in C2C12 cells, but not in macrophages. ADRC-CM also increased CD206+ cells expression and decreased TNF-α in macrophages. Autologous ADRC implantation was safe and effective in patients with CLI and could repair damaged tissue via its ability to promote angiogenesis and suppress tissue inflammation.