Bong-Sung Kim

The macrophage migration inhibitory factor protein superfamily in obesity and wound repair

The rising number of obese individuals has become a major burden to the healthcare systems worldwide. Obesity includes not only the increase of adipose tissue mass but importantly also the altered cellular functions that collectively lead to a chronic state of adipose tissue inflammation, insulin resistance and impaired wound healing. Adipose tissue undergoing chronic inflammation shows altered cytokine expression and an accumulation of adipose tissue macrophages (ATM). The macrophage migration inhibitory factor (MIF) superfamily consists of MIF and the recently identified homolog D-dopachrome tautomerase (D-DT or MIF-2). MIF and D-DT, which both bind to the CD74/CD44 receptor complex, are differentially expressed in adipose tissue and have distinct roles in adipogenesis. MIF positively correlates with obesity as well as insulin resistance and contributes to adipose tissue inflammation by modulating ATM functions. D-DT, however, is negatively correlated with obesity and reverses glucose intolerance. In this review, their respective roles in adipose tissue homeostasis, adipose tissue inflammation, insulin resistance and impaired wound healing will be reviewed.

The effect of mechanical stress on the proliferation, adipogenic differentiation and gene expression of human adipose-derived stem cells.

To allow for a better implementation of external volume expansion to clinical applications for soft tissue regeneration, it is necessary to comprehensively understand the underlying mechanisms. As human adipose‐derived stem cells (hASCs) play a crucial role in soft tissue enlargement, we investigated the impact of cyclic stretch on gene expression, proliferation rate and adipogenic differentiation of these cells. After cyclic stretching, RNA was extracted and subjected to DNA microarray analysis and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Also, the expression of FABP4 mRNA was analysed by RT‐qPCR to test whether mechanical stretch affected adipogenic differentiation of hASCs. The proliferation rate was assessed using the alamarBlue assay and Ki‐67 staining. A cell cycle analysis was performed with flow cytometry and Western blot. We found that cyclic stretch significantly induced the expression of CYP1B1 mRNA. Furthermore, the adipogenic differentiation of hASCs was impaired, as was the proliferation. This was partly due to a decrease in extracellular signal‐regulated kinase (ERK) 1/2 and histone H3 phosphorylation, suggesting a growth arrest in the G2/M phase of the cell cycle. Enrichment analyses demonstrated that stretch‐regulated genes were over‐represented in pathways and biological processes involved in extracellular matrix organization, vascular remodelling and responses to cell stress. Taken together, mechanical stress impaired both proliferation and adipogenic differentiation, but led to a tissue‐remodelling phenotype of hASCs. These data suggest that extracellular matrix remodelling and neoangiogenesis may play a more important role in external volume expansion than proliferation and adipogenesis of hASCs. Copyright

Microcirculation in open vs. minimally invasive dorsal stabilization of thoracolumbar fractures

Standard open and percutaneous minimally invasive surgical procedures co-exist in the treatment of fractures of the thoracolumbar spine. Shorter skin incisions just above the pedicles are used in minimally invasive procedures. Full-length skin incisions and invasive preparations are applied in the standard open approach. While both methods show equivalent rates of intraoperative surgical complications and comparable clinical and radiological outcomes, blood loss and operation time have shown to be decreased in minimally invasive treatment. However, no study so far has investigated differences in microcirculation. This study hypothesized less impairment of microcirculation in the minimally invasive approach compared to the open approach and an improvement of microcirculation over time. A prospective cohort study was conducted using non-invasive laser-Doppler spectrophotometry (an O2C “oxygen to see” device) for measurement of cutaneous and subcutaneous blood oxygenation (SO2), haemoglobin concentration (Hb), and blood flow at depths of 2, 8, and 15 mm at six locations on the skin. Measurements were performed before surgery, 8 and 24 h after surgery, and 2, 4, 7, 12 and 20 days after surgery, however the number of patients measured decreased towards the later time points. Forty patients were included in the study, 20 with each approach (18 females and 22 males). Pair-wise comparison of the types of surgical procedure for each measurement point revealed a significantly higher flow value in the minimally invasive group at one of the measurement points located between the incisions (P = .041). The point-wise analyses of SO2 and Hb did not show significant differences between the approaches. In conclusion, significantly albeit moderately higher flow values could be found in minimally invasive procedures compared to open operations of thoracolumbar fractures in the area of skin that is spared by the incisions.

The Effect of Antiseptics on Adipose-Derived Stem Cells

Background: Although chemical antiseptics are the most basic measure to control wound infection and frequently come into contact with subcutaneous adipose tissue, no studies have evaluated their toxicity on adipose tissue and its cell fractions. In the present study, the effects of five different antiseptics on adipose-derived stem cells were evaluated. Methods: Human adipose-derived stem cells were harvested from healthy donors. Adipose-derived stem cell viability was measured after treatment with different concentrations of antiseptics over 5 days. Furthermore, the effect on the proliferation, adipogenic differentiation, and apoptosis/necrosis of adipose-derived stem cells was analyzed. Finally, the mRNA expression of the stem cell markers CD29, CD34, CD73, CD90, and CD105 was detected. Results: Octenisept and Betaisodona significantly reduced cell proliferation and differentiation and led to considerable adipose-derived stem cell necrosis. Octenisept decreased stem cell viability at the lowest concentrations tested, and all stem cell markers were down-regulated by Octeniseptr and Betaisodona. Lavasept and Prontosan both led to reduced stem cell viability, proliferation, and differentiation, and increased apoptosis/necrosis, although the effects were less pronounced compared with Octenisept and Betaisodona. Adipose-derived stem cells survived treatment with mafenide acetate even at high concentrations, and mafenide acetate showed minimal negative effects on their proliferation, adipogenic differentiation, cell death, and stem cell marker expression. Conclusions: Mafenide acetate may be regarded as a feasible antiseptic for the treatment of wounds with exposed adipose tissue because of its low adipose-derived stem cell toxicity. Lavasept and Prontosan are possible alternatives to mafenide acetate. Octenisept and Betaisodona, by contrast, may be used only in highly diluted solutions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Pre-expanded Supraclavicular Artery Perforator Flap

The supraclavicular artery perforator (SAP) flap is a versatile flap for the reconstruction of head and neck defects. Recently, the authors have modified the SAP flap by using an anterior branch of the transverse cervical artery. The anterior SAP flap allows the harvest of a tissue island in the deltopectoral fossa, which is even thinner, is more pliable, and shows a superior color match to the face and neck compared with the original SAP flap. Pre-expansion increases flap size considerably, enabling the coverage of extended defects without the need of microsurgery.

Spontaneous Reinnervation of Deep Inferior Epigastric Perforator Flaps after Delayed Breast Reconstruction

BACKGROUND The spontaneous reinnervation of free flaps, such as deep inferior epigastric perforator (DIEP) flaps, is not fully understood, and few publications have investigated this issue. The aim of this study was to examine spontaneous reinnervation following breast reconstruction with autologous DIEP flaps without an additional nerve transfer. METHODS In a retrospective clinical study, 18 female patients were investigated for a mean of 49.59 months (range, 12-88 months) following breast reconstruction with a unilateral DIEP flap. Five sensory modalities were tested: pressure perception, dynamic two-point discrimination, sharp-blunt discrimination, hot and cold discrimination, and vibration perception threshold (VPT). The measurements were performed on the reconstructed breast, flap surrounding transition zone, healthy contralateral breast, and the donor site. For a more precise analysis all breasts have been divided into five different segments (mediocranial, laterocranial, mediocaudal, laterocaudal, and reconstructed nipple-areola complex, if present). Additionally, tissue oxygen saturation and tissue hemoglobin were measured by laser Doppler spectroscopy. RESULTS Spontaneous reinnervation of at least one modality tested was observed in all DIEP flaps (n = 18). This sensitive recovery increases over the postoperative period. The maximum difference between the controls and DIEP flaps was observed in cold perception, whereas the least difference was observed in the VPT. Regarding the different segments, we observed better sensitive recovery in the cranial parts of the DIEP flaps and the transition zone. CONCLUSION This study provides certain predictions for patients and surgeons, when and to which extent spontaneous reinnervation can be expected.

Adipose Tissue Increases the Proliferation of Melanoma Cell Lines In Vitro.

Introduction:Autologous fat grafting has been used for reconstructive and aesthetic surgery for more than a century. Although initial criticism involved fat resorption and later the possible radiological interference in mammographies, the most recent debate focuses on the carcinogenicity of fat grafts. Among malignant skin tumors, melanomas show the highest lethality and lead to significant soft tissue defects after resection with fat grafting representing a feasible therapy option for tissue reconstruction. In contrast to breast carcinoma, little data is available regarding the carcinogenicity of fat grafts in melanoma patients. The present study was designed to investigate the influence of whole adipose tissue on the growth of melanoma cell lines compared to breast cancer cell lines. Methods:Human subcutaneous adipose tissue was obtained from elective surgeries and cut into pieces ranging from 20 to 500 mg. Adipose tissue samples were co-cultivated with the human breast cancer cell line MCF-7 and the melanoma cell lines MEL-JUSO and IGR-37, and proliferation was measured using the alamarBlue proliferation assay. Additionally, the same experiment was conducted under nutrient-limited conditions. Results:We found that adipose tissue significantly increased the proliferation of the human breast cancer cell line MCF-7 and importantly also of the melanoma cell lines MEL-JUSO and IGR-37 under optimal nutrient supply. Although the impact of adipose tissue on the growth of MCF-7 cells under nutrient deprivation was comparatively weak, the proliferation of MEL-JUSO and IGR-37 cells was clearly stimulated by adipose tissue. Discussion:Our results show that adipose tissue enhances not only the growth of breast cancer but also melanoma cells even under conditions of nutrient limitation by soluble factors secreted by adipose tissue. With respect to our results and the current literature, reconstruction of soft tissue defects after malignancies including breast cancer and melanoma should be conducted with great care and only after complete tumor resection.

Macrophage Migration Inhibitory Factor - A Favorable Marker in Inflammatory Diseases?

BACKGROUND Macrophage migration inhibitory factor (MIF) was firstly described in the 1960s as a pleiotropic cytokine affecting a variety of immune cells. Different physiological functions mainly involving inflammatory reactions such as chemokine-like function and regulating systemic stress responses have been reported. OBJECTIVE In several clinical studies the use of MIF as a biomarker has been investigated promising support for diseases with an inflammatory aspect such as sepsis, systemic infections and autoimmune diseases. This article in detail reviews clinical data and evaluates the function as biomarker focusing on inflammatory and autoimmune diseases. CONCLUSION Recent studies suggest MIF to be a marker for different inflammatory diseases and might serve as therapeutic target in the future.

Commentary on: Interaction Between Breast Cancer Cells and Adipose Tissue Cells Derived from Fat Grafting

We appreciate the opportunity to comment on the article entitled “Interaction Between Breast Cancer Cells and Adipose Tissue Cells Derived from Fat Grafting” by Massa et al.1 The authors investigated a controversial topic that has polarized plastic surgeons for many years, namely the role of fat grafting in carcinogenesis. In a common in vitro model, undigested adipose tissue, cells of the stromal vascular fraction (SVF) with or without induction of adipogenic differentiation, were cocultured with three different breast-cancer cell lines in a Boyden chamber. Bone-marrow-derived stroma cells served as a control. The results show that the proliferation of all three cancer cell lines was induced by whole adipose tissue, in vitro differentiated adipocytes, and, to a lesser extent, noninduced SVF cells. The present study represents an effort to shed light into the pathomechanisms of adipose tissue-fueled cancer development. We have recently shown that adipose tissue not only promotes breast cancer but also other cancer entities such as melanoma in a comparable experimental setting.2 It is a feasible approach to compare the cancer-proliferative character of adipose tissue, differentiated adipocytes, and SVF cells and to compare them to a nonadipogenic control. Although the present study certainly enriches our knowledge of the carcinogenicity of fat, we want …

The Effect of Lipoaspirates on Human Keratinocytes

BACKGROUND One increasingly important trend in plastic, reconstructive, and aesthetic surgery is the use of fat grafts to improve cutaneous wound healing. In clinical practice, lipoaspirates (adipose tissue harvested by liposuction) are re-injected in a procedure called lipofilling. Previous studies, however, mainly evaluated the regenerative effect of isolated adipocytes, adipose-derived stem cells, and excised en bloc adipose tissue on keratinocytes, whereas no study to date has examined the effect of lipoaspirates. OBJECTIVES The authors aimed to investigate differences in the regenerative property of en bloc adipose tissue and lipoaspirates on keratinocytes. METHODS Human keratinocytes, lipoaspirates, and en bloc adipose tissue from 36 healthy donors were isolated. In vitro proliferation, differentiation, migration, stratification, and wound healing of keratinocyte monolayers were measured. Furthermore, secreted levels of VEGF, bFGF, IGF-1, MMP-9, and MIF were detected by ELISA. RESULTS Migration, proliferation, and wound healing of keratinocytes were increased by lipoaspirates. Interestingly, the effect of lipoaspirates on keratinocyte proliferation was significantly higher than by en bloc adipose tissue after 5 days. The differentiation of keratinocytes was equally attenuated by lipoaspirates and en bloc adipose tissue. Stratification of keratinocyte layers was enhanced by lipoaspirates and en bloc fat when compared to controls. Lipoaspirates secrete higher levels of bFGF, whereas higher levels of VEGF and IGF-1 are released by en bloc adipose tissue. CONCLUSION We show that lipoaspirates and en bloc adipose tissue have a regenerative effect on keratinocytes. One reason for the higher effect of lipoaspirates on keratinocyte proliferation may be the secretion of different cytokines.