Adipose tissue derived stromal vascular fraction as an adjuvant therapy in stroke rehabilitation: Case reports.

INTRODUCTION: Stroke often causes residual hemiparesis, and upper extremity motor impairment is usually more disabling than lower extremity in those who are suffering from post-stroke hemiparesis. Cell therapy is one of the promising therapies to reduce post-stroke disability. PATIENT CONCERNS: Three male participants were included in the study to investigate the feasibility and tolerability of autologous adipose tissue derived stromal vascular fraction. DIAGNOSIS: All participants had hemiparesis after 1st-ever stroke longer than 6 months previously. INTERVENTIONS: Under general anesthesia, liposuction of abdominal subcutaneous fat was performed. Stromal vascular fraction freshly isolated from the adipose tissue extract was injected into the muscles of paretic upper extremity. All participants received inpatient stroke rehabilitation consisted of physical and occupational therapy more than 3 hours a day for 2 months or more. OUTCOMES: The whole procedure did not produce any significant adverse event in all participants. Adipose tissue extracts yielded sufficient stromal cells. One participant showed clinically important change in upper extremity Fugl-Meyer assessment after the injection and it lasted up to 6 months. Functional magnetic resonance imaging showed concomitant increase in ipsilesional cortical activity. The other 2 participants did not show remarkable changes. LESSONS: Intramuscular injection of autologous adipose tissue derived stromal vascular fraction seems to be a safe and tolerable procedure in subjects with chronic stroke, and its utility in rehabilitation needs further investigation.

Hypoxia Rapidly Induces the Expression of Cardiomyogenic Factors in Human Adipose-Derived Adherent Stromal Cells.

BACKGROUND: The efficacy of interstitial vascular fraction (SVF) transplantation in the treatment of heart disease has been proven in a variety of in vivo studies. In a previous study, we found that bone marrow-derived mesenchymal stem cells (BM-MSCs) altered their expression of several cardiomyogenic factors under hypoxic conditions. METHODS: We hypothesized that hypoxia may also induce obtained adipose-derived adherent stromal cells (ADASs) from SVFs and adipose-derived stem cells (ASCs) to differentiate into cardiomyocytes and/or cells with comparable phenotypes. We examined the differentiation markers of cell lineages in ADASs and ASCs according to time by hypoxic stress and found that only ADASs expressed cardiomyogenic markers within 24 h under hypoxic conditions in association with the expression of hypoxia-inducible factor 1-α (HIF-1α). RESULTS: Differentially secreted proteins in a conditioned medium (CM) from ASCs and ADASs under normoxic or hypoxic conditions were detected using an antibody assay and may be associated with a dramatic increase in the expression of cardiomyogenic markers in only ADASs. Furthermore, the cardiomyogenic factors were expressed more rapidly in ADASs than in ASCs under hypoxic conditions in association with the expression of HIF-1α, and angiogenin, fibroblast growth factor-19 (FGF-19) and/or macrophage inhibitory factor (MIF) are related. CONCLUSIONS: These results provide new insights into the applicability of ADASs preconditioned by hypoxic stress in cardiac diseases.

Anti-apoptotic effects of adipose-derived adherent stromal cells in mesenchymal stem cells exposed to oxidative stress.

Adipose-derived stromal vascular fractions (SVFs) are a heterogeneous collection of cells, and their regenerative modality has been applied in various animal experiments and clinical trials. Despite the attractive advantages of SVFs in clinical interventions, the recent status of clinical studies involving the application of SVFs in many diseases has not been fully evaluated. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types despite their low numbers in heart tissue. Here, we sought to determine if SVF implantation into impaired heart tissue affected endogenous MSCs in the heart. Therefore, we investigated the expression levels of proteins associated with oxidation, inflammation, and apoptosis in MSCs co-cultured with adipose-derived adherent stromal cells (ADASs) from 6 donors' SVFs under oxidative stress conditions for their roles in many physiological processes in the heart. Interestingly, p53 pathway proteins and mitogen-activated protein kinase (MAPK) signalling pathway components were up-regulated by H2 O2 but exhibited a downward trend in MSCs co-cultured with ADASs. These data suggest that ADASs may inhibit oxidative stress-induced apoptosis in MSCs via the p53 and MAPK pathways. Our findings also suggest that the positive effects of SVF implantation into damaged heart tissue may be attributed to the various responses of MSCs. This finding may provide new insights for the clinical application of adipose-derived SVF transplantation in cardiac diseases. SIGNIFICANCE OF THE STUDY: We investigated the expression levels of proteins associated with oxidation, inflammation, and apoptosis in MSCs co-cultured with isolated ADASs from 6 donors' SVFs under oxidative stress conditions. Our results imply that isolated ADASs from SVFs may inhibit oxidative stress-induced cell cycle arrest and/or apoptosis in MSCs via a p53-dependent pathway. Furthermore, we identified an anti-apoptotic mechanism involving oxidative stress-induced apoptosis by adipose-derived ADASs in MSCs for the first time. Our findings suggest that the positive effects of SVF implantation into damaged heart tissue may be attributed to the various actions of MSCs.

Combination Therapy Comprising a Static Magnetic Field with Contractility Improves Skin Wounds.

Cutaneous wounds can present significant clinical problems because of abnormal healing after deep dermal damage. Despite technical advances in wound care, there are still unmet needs that result from inefficient treatment. In this study, we aimed to improve skin wound healing using a contractibility band with static magnetic field (SMF), termed a magnetic band (Mb). To examine the effect of the Mb on wound healing, full-thickness 15 × 35 mm excision wounds were surgically created on the dorsum of rats. An elastic and contractile band (nontreatment), or one neodymium magnet (Nd-1) or two magnets with an elastic and contractile band (Nd-2) were topically applied to the wound daily and the wound size was measured from day 1 to 7 after surgery. Nd-2 showed a significant (95%) reduction in the wound size on day 3. Histological analysis showed that proinflammatory cytokine levels were diminished by Nd-2, and granulation tissue and microvessels were increased compared with those in the sham group. During Mb-induced wound healing, apoptosis was significantly reduced and matrix remodeling-related factors were initially regulated. The results suggest that combination therapy comprising an SMF and an elastic and contractile band could be a promising tool to heal cutaneous wounds rapidly.

Effects of donor age on human adipose-derived adherent stromal cells under oxidative stress conditions.

Objective Adipose-derived stromal vascular fractions (SVFs) are heterogeneous complex populations of cells with therapeutic efficacy for tissue generation and vascular stabilization. SVFs have cardiomyogenic potential, and many researchers have examined the possibility of SVF transplantation for heart disease. In cell-based therapies, donor age affects the regenerative capability, cell yield, and differentiation potential of adult tissues; however, opposing or controversial results have been found in humans. We examined whether SVF transplantation into impaired heart tissue shows differential effects according to donor age. Methods We investigated differences in protein expression in human umbilical vein endothelial cells (HUVECs) co-cultured with adipose-derived adherent stromal cells (ADASs) from donors of different ages [>40-year-olds (40s group) and >60-year-olds (60s group)] under oxidative stress conditions. Results Although co-culturing HUVECs with ADASs ameliorated inflammation due to increased oxidative stress conditions, few differences were observed between the ADASs from the 40s and 60s groups. Moreover, the Database for Annotation, Visualization, and Integrated Discovery classification tool revealed differentially expressed genes in the Kyoto Encyclopedia of Genes and Genomes pathway associated with cytokine-cytokine receptor interaction in response to ADASs. Conclusion Protein expression profiles were unchanged in HUVECs induced by isolated ADASs from donors of different ages under oxidative stress conditions.

Rapid Induction of Osteogenic Markers in Mesenchymal Stem Cells by Adipose-Derived Stromal Vascular Fraction Cells.

BACKGROUND/AIMS: Stromal vascular fraction (SVF) cells are a mixed cell population, and their regenerative capacity has been validated in various therapeutic models. The purpose of this study was to investigate the regenerative mechanisms utilized by implanted SVF cells. Using an in vitro co-culture system, we sought to determine whether SVF implantation into impaired tissue affects endogenous mesenchymal stem cell (MSC) differentiation; MSCs can differentiate into a variety of cell types, and they have a strong regenerative capacity despite their low numbers in impaired tissue. METHODS: Adipose-derived SVF cells obtained from four donors were co-cultured with bone marrow-derived MSCs, and the differential expression of osteogenic markers and osteogenic differentiation inducers over time was analyzed in mono-cultured MSCs and MSCs co-cultured with SVF cells. RESULTS: The co-cultivation of MSCs with SVF cells significantly and mutually induced the expression of osteogenic-specific markers via paracrine and/or autocrine regulation but did not induce adipocyte, chondrocyte or myoblast marker expression. More surprisingly, subsequent osteogenesis and/or comparable effects were rapidly induced within 48 h. CONCLUSION: To the best of our knowledge, this is the first study in which osteogenesis and/or comparable effects were rapidly induced in bone marrow-derived MSCs and adipose-derived SVF cells through co-cultivation. Our findings suggest that the positive effects of SVF implantation into impaired bone may be attributed to the rapid induction of MSC osteogenesis, and the transplantation of co-cultured and preconditioned SVF cells and/or MSCs may be more effective than the transplantation of untreated cells for the treatment of bone defects.

Gender-dimorphic effects of adipose-derived stromal vascular fractions on HUVECs exposed to oxidative stress.

Stromal vascular fractions (SVFs) are a heterogeneous collection of cells within adipose tissue that are being studied for various clinical indications. In this study, we aimed to determine whether SVF transplantation into impaired tissues has differential effects on inflammatory and angiogenetic properties with regard to gender. As reactive oxygen species have been implicated in cardiovascular disease development, we investigated differences in gene and protein expression related to inflammation and angiogenesis in HUVECs co-cultured with adipose-derived SVFs from male (M group) and female (F group) individuals under oxidative stress conditions. The expression of several inflammatory (interleukin (IL)-33) and angiogenetic (platelet-derived growth factor (PDGF)) factors differed dramatically between male and female donors. Anti-inflammatory and pro-angiogenetic responses were observed in HUVECs co-cultured with SVFs under oxidative stress conditions, and these characteristics may exhibit partially differential effects according to gender. Using network analysis, we showed that co-culturing HUVECs with SVFs ameliorated pyroptosis/apoptosis via an increase in oxidative stress. Activation of caspase-1 and IL-1B was significantly altered in HUVECs co-cultured with SVFs from female donors. These findings regarding gender-dimorphic regulation of adipose-derived SVFs provide valuable information that can be used for evidence-based gender-specific clinical treatment of SVF transplantation for understanding of cardiovascular disease, allowing for the development of additional treatment.

Mini-breast reconstruction with an omental flap: a retrospective clinical study.

INTRODUCTION: Potential challenges associated with immediate small breast reconstruction include an inadequate size of the donor site, a thinner skin envelope and limited selection of implants. We present immediate postmastectomy reconstruction of small breasts with a laparoscopically harvested pedicled omental flap (LHPOF) in five Korean women. METHODS: From December 2014 to July 2015, we performed immediate postmastectomy reconstruction with an LHPOF in five breast cancer patients. Data on the patients' age; body mass index; tumour size; site, type and weight of the mastectomy specimen; operative time; hospital stay; complications; postoperative chemotherapy or radiation therapy; and follow-up duration were reviewed in this retrospective clinical study. RESULTS: The mean mastectomy specimen weight was 212 g (range: 104-272 g). The mean operative time was 298 min (range: 240-380 min), and the mean harvesting time was 75 min (range: 65-90 min). There were no flap-related complications such as fat necrosis or flap loss and no donor site-related complications such as bowel dysfunction, an epigastric bulge or hernia during the follow-up period (average: 8.2 months, range: 5-11 months). The cosmetic results were satisfactory. DISCUSSION: The LHPOF can be useful for immediate postmastectomy reconstruction of small breasts, because it provides a soft and naturally ptotic appearance of the reconstructed breast (versus implant-based reconstruction) with low donor-site morbidity (versus other autologous tissue reconstruction approaches).

Blending of the lateral deep slip of the platysma muscle into the buccinator muscle.

PURPOSE: The aim of this study was to clarify the prevalence of blending of the lateral deep slip of the platysma into the buccinator, and the morphologic and spatial relationships thereof. METHODS: The lateral deep slip of the platysma was investigated in 42 specimens of embalmed adult Korean cadavers. RESULTS: The lateral deep slip of the platysma was observed in 17 of the 42 specimens (40.5 %). When present, it divided from the deep portion (16 specimens, 38.1 %) or the lateral portion (1 specimen, 2.4 %) of the platysma pars modiolaris. The lateral deep slip passed deep to the facial artery, where it blended into the inferior part of the buccinator. The blending site was located inferolateral to the modiolus. After blending into the buccinator, the fibers of the lateral deep slip coursed longitudinally with the inferior fibers of the buccinator. CONCLUSION: The present description of the topography of the lateral deep slip of the platysma and its relationship with surrounding structures could improve the understanding of the detailed movements of the lower face and the related EMG activities, with the data also being useful when performing facial surgery.

Nasal anthropometry on facial computed tomography scans for rhinoplasty in koreans.

BACKGROUND: Cephalometric analysis is essential for planning treatment in maxillofacial and aesthetic facial surgery. Although photometric analysis of the Korean nose has been attempted in the past, anthropometry of the deeper nasal structures in the same population based on computerized tomography (CT) has not been published. We therefore measured three anthropometric parameters of the nose on CT scans in our clinical series of patients. METHODS: We conducted the current retrospective study of a total of 100 patients (n=100) who underwent a CT-guided radiological measurement at our institution during a period ranging from January of 2008 to August of 2010. In these patients, we took three anthropometric measurements: the nasofrontal angle, the pyramidal angle, and the linear distance between the nasion and the tip of the nasal bone. RESULTS: The mean nasofrontal angle was 131.14° in the male patients and 140.70° in the female patients. The mean linear distance between the nasion and the tip of the nasal bone was 21.28 mm and 18.02 mm, respectively. The mean nasal pyramidal angle was 112.89° and 103.25° at the level of the nasal root, 117.49° and 115.60° at the middle level of the nasal bone, and 127.99° and 125.04° at the level of the tip of the nasal bone, respectively. CONCLUSIONS: In conclusion, our data will be helpful in the preparation of silicone implants for augmentation and/or corrective rhinoplasty in ethnic Korean people.

Elbow reconstruction using island flap for burn patients.

BACKGROUND: Deep burns of the elbow lead to soft tissue necrosis and infection, with exposure of deep structures. Adequate wound coverage of this area requires thin, pliable, and durable tissue, while optimal functional recovery requires early coverage and functional rehabilitation. We have found 3 types of island flaps that provide reliable coverage for the elbow. METHODS: A retrospective study was performed on all patients who underwent flap coverage of an elbow defect at our hospital. The patients' data including age, sex, cause of injury, wound dimensions, timing of flap coverage, postoperative elbow motion, and complications were investigated. RESULTS: Between 2001 and 2012, 16 patients were treated at our hospital. The mean age was 53.3 years. Three kinds of flaps were performed: 9 latissimus dorsi flaps, 4 lateral arm flaps, and 4 radial forearm flaps. The average defect size was 183.5 cm(2) (range, 28 to 670 cm(2)). Wound coverage was performed at mean duration of 45.9 days (range, 14 to 91 days). The mean postoperative active elbow flexion was 98° (range, 85° to 115°). Partial flap failure occurred in 1 latissimus dorsi flap. Minor complications included partial flap loss (11.8%), hematoma (23.5%), seroma (35.3%), and wound infection (5.9%). CONCLUSIONS: Flap selection for elbow reconstruction is determined by the defect size and the extent of the adjacent tissue injury. Elbow reconstruction using an island flap is a single-staged, reliable, and relatively simple procedure that permits initiation of early rehabilitation, thereby improving a patient's functional outcome.

Case Reports of Adipose-derived Stem Cell Therapy for Nasal Skin Necrosis after Filler Injection.

With the gradual increase of cases using fillers, cases of patients treated by non-medical professionals or inexperienced physicians resulting in complications are also increasing. We herein report 2 patients who experienced acute complications after receiving filler injections and were successfully treated with adipose-derived stem cell (ADSCs) therapy. Case 1 was a 23-year-old female patient who received a filler (Restylane) injection in her forehead, glabella, and nose by a non-medical professional. The day after her injection, inflammation was observed with a 3×3 cm skin necrosis. Case 2 was a 30-year-old woman who received a filler injection of hyaluronic acid gel (Juvederm) on her nasal dorsum and tip at a private clinic. She developed erythema and swelling in the filler-injected area A solution containing ADSCs harvested from each patient's abdominal subcutaneous tissue was injected into the lesion at the subcutaneous and dermis levels. The wounds healed without additional treatment. With continuous follow-up, both patients experienced only fine linear scars 6 months postoperatively. By using adipose-derived stem cells, we successfully treated the acute complications of skin necrosis after the filler injection, resulting in much less scarring, and more satisfactory results were achieved not only in wound healing, but also in esthetics.

Reconstruction of fingertip and stump using a composite graft from the hypothenar region.

Finger amputation with bone exposure when replantation is not feasible requires a procedure for closure and padding of the stump. To preserve the length and provide adequate coverage, various flaps are used. A situation may occur in which local flaps are not sufficient and distant flaps are preferred. However, distant flaps often require a two-stage procedure, prolonged immobilization, and skin grafts. Thus, a simpler approach for fingertip or stump reconstruction while maintaining the padding effect of a flap was designed. The composite of glabrous skin and subcutaneous fat provided such padding, was performed in a single stage, and the donor site morbidity was negligible. During a 5-year period from 1996 to September 2002, 15 cases of finger stumps were reconstructed using the hypothenar composite graft. The age of the patients ranged from 1 to 63 years (average, 30 years). The average follow-up was 35 months. The donor sites were closed primarily and there were no marked complications related to this site. The graft showed relatively good contour and color match to the adjacent field, with an average two-point discrimination of 5.7 mm, indicating satisfactory reinnervation. The hypothenar composite graft for reconstruction of finger stumps can provide protective padding, maximal stump length, and minimal donor site morbidity, leading to satisfactory aesthetic and functional recovery.

Coverage of difficult wounds around the knee joint with prefabricated, distally based sartorius muscle flaps.

The coverage of soft-tissue defects around the knee joint presents a difficult challenge to the reconstructive surgeon. Various reconstructive choices are available depending on the location, size, and depth of the defect relative to the knee joint. However, the knee joint frequently accompanies injuries to the lower leg that may limit the use of muscle flaps, especially the gastrocnemius muscle. The use of a free flap is preferred for reconstruction involving obliteration of large-cavity defects, but the isolation of recipient pedicle can be difficult because of the extent of injury zone and in cases of chronic infection around the knee. To provide muscle bulk with a reliable vascular supply, the distally based, prefabricated sartorius muscle flap was used as a last resort to reconstruct difficult wounds with chronic osteomyelitis around the knee joint in 6 patients from June 1995 to May 2001. This method is a two-stage procedure. First, the sartorius muscle is prefabricated by denervation and vascular delay. Silicone sheets are used to increase the vascularity and dimension of the flap. Second, after 3 weeks, the muscle is transposed based on a distal pedicle to reconstruct the soft-tissue defect around the knee. The prefabricated sartorius muscle can provide efficient bulk to obliterate the dead space and to cover moderate-size soft-tissue defects around the knee joint. This method can be considered to reconstruct the soft tissue around the knee joint when local muscle flaps and free flaps are not feasible.