Comparison between Stromal Vascular Fraction and Adipose Mesenchymal Stem Cells in Remodeling Hypertrophic Scars.

Hypertrophic scars (HTS) are characterized by excessive amount of collagen deposition and principally occur following burn injuries or surgeries. In absence of effective treatments, the use of mesenchymal stem/stromal cells, which have been shown to attenuate fibrosis in various applications, seems of interest. The objectives of the present study were therefore to evaluate the effect of human adipose tissue-derived mesenchymal stem cells (hASC) on a pre-existing HTS in a humanized skin graft model in Nude mice and to compare the efficacy of hASCs versus stromal vascular fraction (SVF). We found that injection of SVF or hASCs resulted in an attenuation of HTS as noticed after clinical evaluation of skin thickness, which was associated with lower total collagen contents in the skins of treated mice and a reduced dermis thickness after histological analysis. Although both SVF and hASCs were able to significantly reduce the clinical and histological parameters of HTS, hASCs appeared to be more efficient than SVF. The therapeutic effect of hASCs was attributed to higher expression of TGFß3 and HGF, which are important anti-fibrotic mediators, and to higher levels of MMP-2 and MMP-2/TIMP-2 ratio, which reflect the remodelling activity responsible for fibrosis resorption. These results demonstrated the therapeutic potential of hASCs for clinical applications of hypertrophic scarring.

Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial.

UNLABELLED: : Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 × 10(6) cells), medium dose (10 × 10(6)), and high dose (50 × 10(6)). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy. SIGNIFICANCE: Although this phase I study included a limited number of patients without a placebo arm, it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis. This study also provides encouraging preliminary evidence of efficacy. Larger and controlled long-term studies are now mandatory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis.

Adipose Mesenchymal Stem Cells Isolated after Manual or Water-jet-Assisted Liposuction Display Similar Properties.

Mesenchymal stem or stromal cells (MSC) are under investigation in many clinical trials for their therapeutic potential in a variety of diseases, including autoimmune and inflammatory disorders. One of the main sources of MSCs is the adipose tissue, which is mainly obtained by manual liposuction using a cannula linked to a syringe. However, in the past years, a number of devices for fat liposuction intended for clinical use have been commercialized but few papers have compared these procedures in terms of stromal vascular fraction (SVF) or adipose mesenchymal stromal cells (ASC). The objective of the present study was to compare and qualify for clinical use the ASC obtained from fat isolated with the manual or the Bodyjet(®) water-jet-assisted procedure. Although the initial number of cells obtained after collagenase digestion was higher with the manual procedure, the percentage of dead cells, the number of colony forming unit-fibroblast and the phenotype of cells were identical in the SVF at isolation (day 0) and in the ASC populations at day 14. We also showed that the osteogenic and adipogenic differentiation potentials of ASCs were identical between preparations while a slight but significant higher in vitro immunosuppressive effect was observed with ASCs isolated from fat removed with a cannula. The difference in the immunomodulatory effect between ASC populations was, however, not observed in vivo using the delayed-type hypersensitivity (DTH) model. Our data, therefore, indicate that the procedure for fat liposuction does not impact the characteristics or the therapeutic function of ASCs.

Advances in Research in Animal Models of Burn-Related Hypertrophic Scarring.

Skin burn injuries affect approximately 500,000 people per year in France. After deep burns, functional sequelae associated with hypertrophic and retractile scars are an important public health problem. To understand the pathophysiology of sequelae and evaluate new therapeutic approaches, the use of animal models that should be standard tools is necessary. Some pre-clinical models of hypertrophic scars after burns have been described, but the choice of the appropriate and relevant experimental model is crucial to accurately investigate any therapeutic approach. A variety of hypertrophic scar animal models have been described after burn lesions; none of which being totally satisfactory. The most frequently used is the hypertrophic scar model after skin excision of the ear rabbit, but this model does not reflect burn injuries. The red Duroc pig seems to be the more relevant model of human hypertrophic scarring after burns; however, because of costs and the lack of studies evaluating burn injuries in this species, the domestic pig is most commonly used in burn research. Elevated hypertrophic scars are obtained, but they spontaneously resolve within a year. Although mortality in small animals is higher and creates technical difficulties, many models on nude mice are used in research. Indeed, transplantation of human hypertrophic scar tissue or human skin grafts may induce hypertrophic scarring that can last more than a year permitting additional manipulation and experimentation.

Dermal flaps in breast reduction: prospective study in 100 breasts.

The most common complication of breast reduction with inverted T-scar technique is wound dehiscence at the junction of the vertical and horizontal sutures. In this study, a technique involving three triangular dermal flaps is presented with the results for healing in the junctional T zone. Fifty women were included in a comparative, single-center randomized double-blind prospective study to evaluate the efficiency of the three-triangular dermal-flap technique in healing in the junctional T zone. All patients were seen for follow-up at 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, and 49 days after surgery to evaluate primary healing in the T zone. Average healing time was 19.7 days in the triangular-skin-flap series and 25.48 days in the control series, with a statistically significant difference (p < 0.01). One patient in the triangular-skin-flap series experienced dehiscence in the T zone (2%) versus eight patients (16%) in the control series. A statistically significant difference was noted (p = 0.012). This technique is based on the association of two principles. First, ischemia on the edges as well as skin necrosis is limited by suturing the two superior skin flaps rather than directly suturing the cutaneous angles. In addition, this technique brings an underlying dermal support. Second, the inferior flap width allows fixing two sutures laterally to limit the central tension. This easy technique does not lengthen total operative time and significantly improves healing time. It is applicable to all breast reductions with inverted T scars.

Use of botulinum toxin type A to improve treatment of facial wounds: a prospective randomised study.

BACKGROUND: The tension vectors acting on the wound edges are transmitted to immature collagen fibres synthesised during the normal healing phase. This accounts for scar widening as well as hypertrophic and hyperpigmented scars. The aim of our study was to evaluate whether early injections of botulinum toxin type A (BTA), which induces temporary muscular paralysis, decreases tension vectors on wound edges and enhances scarring of facial wounds. PATIENTS AND METHODS: Thirty patients with facial wounds were enrolled in this study and randomised into two groups with or without injection of BTA within 72 h postoperatively. BTA was injected into the facial muscles directly or indirectly involved in scar widening. Scars were assessed at a 1-year follow-up visit by patients using the Patient Scar Assessment Scale (PSAS) scale, by an independent evaluator using the Observer Scar Assessment Scale (OSAS) and the Vancouver Scar Scale (VSS), and by a board of six experienced medical specialists using the Visual Analogue Scale (VAS) with standardised photographs. RESULTS: At the 1-year visit, 24 patients were reviewed and six patients were lost to follow-up. No statistically significant differences were found between the two groups for the PSAS, OSAS and VSS scores. However, the median VAS rated by the six evaluators was 8.25 for the botulinum toxin-treated group compared with 6.35 for the control group. This result was statistically different, demonstrating improved scarring with BTA. CONCLUSIONS: Thanks to chemoimmobilisation, injections of BTA appear to improve cosmesis of facial wounds. Accordingly, they would be beneficial for use in young patients for wounds without tissue loss, lying perpendicular to the reduced tension lines of the skin of the face.

Reconstruction of anterior scalp defect with V-Y advancement flap pedicled on the temporal fascia superficialis.

Reconstruction of scalp defect can call upon several surgical techniques. Direct joining is used whenever possible, but because of the low laxity of the scalp, other approaches are often required. Several types of autoclosing flaps of the scalp have been described in the literature. In this article, we report the advantages of the island flap pedicled on the superficial temporal fascia, as described by Onishi (2005) in a case report for the reconstruction of an anterior scalp defect.

Spatulated anastomosis with continuous suture in microreconstructive surgery.

In a well-proven criterion standard technique commonly used in cardiovascular surgery for anastomosis, proximal and distal vessels are spatulated to increase the anastomotic surface and improve congruency between the 2 vessels. Anastomosis is performed with continuous suture of the 2 bisected extremities.A review of the current literature has confirmed that our preliminary results were similar to those achieved by surgeons using the simple interrupted suture technique for microsurgical anastomosis.Patency is highly satisfactory with this technique for anastomosis. Moreover, it is a reliable technique requiring shorter total operative time. Hemostasis is easy to control and can be used with vessel diameters as small as 1 mm. For all these reasons, this technique already commonly used in vascular surgery for anastomosis could be interesting in microsurgery as well.

Correlation of images: technique for mandible biomechanics analysis.

Various experimental or physicomathematical methods can be used to calculate the biomechanical behavior of the mandible. In this study, we tested a new tool for the analysis of mandibular surface strain based on the correlation of images. Five fresh explanted human mandibles were placed in a loading device allowing replication of a physiologic biting exercise. Surfaces of the mandibles were prepared with white and black lacquer. Images were recorded by 2 cameras and analyzed with an algorithm to correlate those images. With the Limess Measurement & Software system and VIC 3D software, we obtained data output concerning deformations, strains, and principal strains. This allowed us to confirm strain distribution on the mandibular corpus and to focus on weak points. Image correlation is a new technique to study mandible biomechanics, which provides accurate measurements on a wide bone surface, with high-definition images and without modification of the structure.

Transplantation of adult myoblasts or adipose tissue precursor cells by high-density injection failed to improve reinnervated skeletal muscles.

We previously showed that transfer of adult myoblasts (MB) into cardiotoxin-damaged muscle improved the properties of reinnervated tibialis anterior muscle of rabbits. However, this cell therapy protocol cannot be applied to humans because of the hazardous effects of the myotoxin. To circumvent this approach, we used the recently developed high-density injection technique to autotransplant cultured cells 1 mm from each other into the tibialis anterior muscle without previous cardiotoxin-induced damage. Two months after transection and immediate suture of the common peroneal nerve, we transferred by this technique two types of precursor cells, MB or cells isolated from the adipose tissue stromal vascular fraction. In contrast to our previous results, muscles studied at 4 months showed no benefits in terms of function or morphology, whatever the transferred cells. These results, together with the results of earlier studies, emphasize the importance of delivery methods and the muscle environment in supporting cell integration into host tissues.

Fat microinfiltration autografting for facial restructuring in HIV patients.

INTRODUCTION: Antiretroviral drugs used to treat HIV infection are closely associated with faciocervical and peripheral lipodystrophies. There are several options for surgical treatment of facial lipodystrophy, one of these was described by S. R. Coleman in 1994, the technique of fat transplantation. MATERIAL AND METHODS: A retrospective study of 23 seropositive patients is presented, who were treated according to Coleman's technique. The surgical procedure was evaluated by clinical and CT analysis. The longest follow-up was 3 years. RESULTS: The technique was well tolerated from both a clinical and psychological point of view. 74% were successful. Multiple fat transplantation procedures were required to obtain a satisfactory result for the remaining patients. No complications were observed. DISCUSSION: Coleman's method is very simple. It is performed without using any biomaterial. There are aesthetic and social benefits for the patients. A limitation of this procedure is that some patients do not have enough fat at the donor site. CONCLUSION: The results of this procedure after a maximum of 3 years postoperatively have been positive. However, there is a need of long-term experience with this method.