Therapeutic Potential and Challenges of Mesenchymal Stem Cell-Derived Exosomes for Peripheral Nerve Regeneration: A Systematic Review.

Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context, mesenchymal stem cell (MSC)-derived exosomes have emerged as a potential therapeutic option. Thus, the focus of this study was to review currently available data on MSC-derived exosome-mounted scaffolds in peripheral nerve regeneration in order to identify the most promising scaffolds and exosome sources currently in the field of peripheral nerve regeneration. We conducted a systematic review following PRISMA 2020 guidelines. Exosome origins varied (adipose-derived MSCs, bone marrow MSCs, gingival MSC, induced pluripotent stem cells and a purified exosome product) similarly to the materials (Matrigel, alginate and silicone, acellular nerve graft [ANG], chitosan, chitin, hydrogel and fibrin glue). The compound muscle action potential (CMAP), sciatic functional index (SFI), gastrocnemius wet weight and histological analyses were used as main outcome measures. Overall, exosome-mounted scaffolds showed better regeneration than scaffolds alone. Functionally, both exosome-enriched chitin and ANG showed a significant improvement over time in the sciatica functional index, CMAP and wet weight. The best histological outcomes were found in the exosome-enriched ANG scaffold with a high increase in the axonal diameter and muscle cross-section area. Further studies are needed to confirm the efficacy of exosome-mounted scaffolds in peripheral nerve regeneration.

Role of Oxygen and Its Radicals in Peripheral Nerve Regeneration: From Hypoxia to Physoxia to Hyperoxia.

Oxygen is compulsory for mitochondrial function and energy supply, but it has numerous more nuanced roles. The different roles of oxygen in peripheral nerve regeneration range from energy supply, inflammation, phagocytosis, and oxidative cell destruction in the context of reperfusion injury to crucial redox signaling cascades that are necessary for effective axonal outgrowth. A fine balance between reactive oxygen species production and antioxidant activity draws the line between physiological and pathological nerve regeneration. There is compelling evidence that redox signaling mediated by the Nox family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases plays an important role in peripheral nerve regeneration. Further research is needed to better characterize the role of Nox in physiological and pathological circumstances, but the available data suggest that the modulation of Nox activity fosters great therapeutic potential. One of the promising approaches to enhance nerve regeneration by modulating the redox environment is hyperbaric oxygen therapy. In this review, we highlight the influence of various oxygenation states, i.e., hypoxia, physoxia, and hyperoxia, on peripheral nerve repair and regeneration. We summarize the currently available data and knowledge on the effectiveness of using hyperbaric oxygen therapy to treat nerve injuries and discuss future directions.

[Management of patients with complex ear deformities]. / Prise en charge des patients présentant des déformations complexes du pavillon de l'oreille.

Complex ear reconstruction requires specialized multidisciplinary care. Most patients present with microtia, often associated with hearing disorders. The management of these disorders is a priority, and reconstruction of the external ear remains optional. Nowadays, auricular reconstruction is based on the subcutaneous implantation of either autologous cartilage or an allogeneic implant. Autologous reconstruction requires highly specialized surgical expertise and involves harvesting rib cartilage but carries a lower risk of exposure compared to allogeneic implants. Both techniques yield good results with a high success rate and have a positive impact on the social functioning and daily life of patients.

La reconstruction complexe du pavillon auriculaire nécessite une prise en charge multidisciplinaire spécialisée. La majorité des patients nécessitant ce geste présentent une microtie, souvent associée à des troubles de l'audition. La prise en charge de ceux-ci est prioritaire et la reconstruction du pavillon reste facultative. Aujourd'hui, la reconstruction du pavillon se base sur l'implantation sous-cutanée d'une maquette de cartilage autologue ou d'un implant allogène. La reconstruction autologue demande une expertise chirurgicale hautement spécialisée et nécessite un prélèvement de cartilage costal mais présente un risque d'exposition inférieur par rapport à l'implant allogène. Les deux techniques permettent d'atteindre de bons résultats avec un taux de réussite élevé et un effet positif sur le fonctionnement social et le quotidien des patients.

Extensive skin necrosis following total hip arthroplasty performed through the direct anterior approach.

BACKGROUND: Total hip arthroplasty is a widely performed surgical procedure, which enables patients to regain mobility, alleviates pain, and improves overall quality of life. Periarticular multimodal drug infiltration (PAI) is increasingly being used as an effective postoperative pain management, decreasing the systemic consumption of opioids. Extensive postoperative skin necrosis without a deep joint infection as a complication of total hip arthroplasty with PAI has not yet been described. CASE PRESENTATION: A 71-year-old patient who underwent total hip arthroplasty of the right hip for primary osteoarthritis through the Direct Anterior Approach presented postoperatively a large area of necrotic skin at the incision. Joint infection was excluded. An extensive debridement was performed and the tissue defect was reconstructed by a pedicled anterolateral thigh flap. The skin maintained a satisfactory appearance at 1 year postoperatively, and the hip was pain-free with restored ranges of motion. The patient was able to walk with no support and without limitation. CONCLUSION: We address the possible risk factors, discuss the use of epinephrine in PAI and explore possible treatment options for such a complication.

Emerging Strategies for the Biofabrication of Multilayer Composite Amniotic Membranes for Biomedical Applications.

The amniotic membrane (AM) is the innermost part of the fetal placenta, which surrounds and protects the fetus. Due to its structural components (stem cells, growth factors, and proteins), AMs display unique biological properties and are a widely available and cost-effective tissue. As a result, AMs have been used for a century as a natural biocompatible dressing for healing corneal and skin wounds. To further increase its properties and expand its applications, advanced hybrid materials based on AMs have recently been developed. One existing approach is to combine the AM with a secondary material to create composite membranes. This review highlights the increasing development of new multilayer composite-based AMs in recent years and focuses on the benefits of additive manufacturing technologies and electrospinning, the most commonly used strategy, in expanding their use for tissue engineering and clinical applications. The use of AMs and multilayer composite-based AMs in the context of nerve regeneration is particularly emphasized and other tissue engineering applications are also discussed. This review highlights that these electrospun multilayered composite membranes were mainly created using decellularized or de-epithelialized AMs, with both synthetic and natural polymers used as secondary materials. Finally, some suggestions are provided to further enhance the biological and mechanical properties of these composite membranes.

Mesenchymal Stem Cells in Nerve Tissue Engineering: Bridging Nerve Gap Injuries in Large Animals.

Cell-therapy-based nerve repair strategies hold great promise. In the field, there is an extensive amount of evidence for better regenerative outcomes when using tissue-engineered nerve grafts for bridging severe gap injuries. Although a massive number of studies have been performed using rodents, only a limited number involving nerve injury models of large animals were reported. Nerve injury models mirroring the human nerve size and injury complexity are crucial to direct the further clinical development of advanced therapeutic interventions. Thus, there is a great need for the advancement of research using large animals, which will closely reflect human nerve repair outcomes. Within this context, this review highlights various stem cell-based nerve repair strategies involving large animal models such as pigs, rabbits, dogs, and monkeys, with an emphasis on the limitations and strengths of therapeutic strategy and outcome measurements. Finally, future directions in the field of nerve repair are discussed. Thus, the present review provides valuable knowledge, as well as the current state of information and insights into nerve repair strategies using cell therapies in large animals.

[Breast reconstruction after mastectomy: necessity, evolution, techniques and research goals]. / Reconstruction mammaire après mastectomie : nécessité, évolution, techniques et objectifs de recherche.

Breast reconstruction is recognized as an integrated part of breast cancer treatment today. Depending on tumor characteristics, different types of partial and total breast resections are indicated: tumorectomy, nipple/skin sparing or complete mastectomy. Patients' desires, general health status and body shape, as well as the necessity of adjuvant therapies, lead to the individual reconstruction plan. Next to implant-based reconstructions, autologous reconstructions play a great role, including local, pedicled and free flaps as well as autologous fat grafting. In cases of tumorectomy, oncoplastic surgery comes into play: it is the combination of a large tumor resection and immediate breast reconstruction with the remaining breast tissue.

À l'heure actuelle, la reconstruction mammaire est reconnue comme partie intégrante du traitement du cancer du sein. En fonction des caractéristiques tumorales, différents types de résections mammaires sont indiqués : tumorectomie, mastectomie avec épargne du mamelon ou de la peau, ou mastectomie totale. L'état de santé général, la nécessité de thérapies adjuvantes, la morphologie et les souhaits des patientes déterminent le plan de reconstruction. En plus de la reconstruction à base d'implants, celle par lambeaux autologues (lambeaux locaux, pédiculés ou libres), ainsi que le transfert de graisse autologue jouent un rôle important. En cas de tumorectomie, la chirurgie oncoplastique entre en jeu, soit la combinaison d'une résection tumorale importante et d'une reconstruction mammaire immédiate par remaniement de la glande persistante.

[Total knee arthroplasty and soft tissue defect: what are the reconstructive options?] / Prothèse totale de genou et lésion des tissus mous : quelles options pour la reconstruction ?

Wound healing issues are not rare after total knee arthroplasty. While most patients heal with local wound care, a minority is susceptible to develop serious complications such as peri-prosthetic joint infection. If direct closure is not feasible, we recommend a multidisciplinary approach based on the ortho-plastic model to determine the optimal wound closure strategy. Negative pressure wound therapy can be used while waiting for definitive coverage to optimise wound environment. Medial gastrocnemius flap is considered as the gold standard procedure for peri-prosthetic substance loss around the knee.

Les problèmes de cicatrisation ne sont pas rares après l'implantation d'une prothèse totale de genou. La plupart des patients guérissent avec des soins locaux mais une minorité d'entre eux peut développer des complications redoutables allant jusqu'à l'infection périprothétique. Hormis les situations pour lesquelles une fermeture directe de la cicatrice chirurgicale peut être réalisée, nous recommandons une approche multidisciplinaire basée sur le modèle de l'ortho-plastique afin de déterminer la stratégie de reconstruction la plus adaptée. La thérapie par pression négative peut être utilisée pour conditionner la plaie en vue d'un geste de couverture définitive. Le lambeau gastrocnémien médial est considéré comme la procédure de référence pour les pertes de substance périprothétique du genou.

[Management of symptomatic breast hypertrophy and reduction mammaplasty]. / Prise en charge de l'hypertrophie mammaire symptomatique et réduction mammaire.

Breast hypertrophy (macromastia) can cause various symptoms correlated with excessive breast volume and is usually associated with breast ptosis. Symptomatic macromastia can constitute a heavy burden on patient's global health. While conservative therapy does not allow for long term relief, breast reduction mammaplasty is an effective and safe treatment. Multiple techniques have been described, but all rely on common principles. Measures can be taken to lower surgical complications rates and implemented by primary care physicians in collaboration with the plastic surgery approach.

L'hypertrophie mammaire symptomatique se définit comme un ou plusieurs symptômes en lien avec un volume mammaire augmenté, en général associé à une ptose mammaire. Elle peut avoir un impact majeur sur la santé globale des patientes. Alors que les traitements conservateurs ne permettent pas de soulager les patientes à long terme, la réduction mammaire chirurgicale est un traitement efficace et sûr. De nombreuses techniques ont été décrites, mais reposent sur des principes communs. Certaines mesures permettent une diminution des risques de complications chirurgicales et peuvent être entreprises conjointement à la prise en charge en chirurgie plastique.

Trametinib after disease reactivation under dabrafenib in Erdheim-Chester disease with both BRAF and KRAS mutations.

Major advances have been made in understanding the pathogenesis of Erdheim-Chester disease (ECD) leading to novel treatment strategies. Targeted therapies such as BRAF inhibition have shown a significant impact on disease management, emphasizing the importance of the activated mitogen-associated protein kinase pathway in this disease. However, incomplete responsiveness, potentially limiting adverse effects, and the occurrence of treatment resistance to BRAF inhibition observed in other BRAF-mutant malignancies imply the importance of therapeutic strategies beyond BRAF inhibition. We report a patient with ECD who carried the BRAFV600E mutation and developed treatment resistance under BRAF inhibition despite initial treatment response. Genetic analyses of a newly developing ECD lesion revealed a somatic KRASQ61H mutation without the presence of BRAFV600E Accordingly, the addition of MEK-inhibiting trametinib to BRAF-inhibiting dabrafenib was able to overcome acquired partial treatment resistance. This is the first report of treatment resistance as a result of a secondary MAPK pathway-activating mutation during BRAF inhibition in ECD. This case contributes to the ongoing efforts of simultaneous BRAF/MEK inhibition as a promising strategy in ECD.

Improved Adipocyte Viability in Autologous Fat Grafting With Ascorbic Acid-Supplemented Tumescent Solution.

INTRODUCTION: In reconstructive surgery, fat volume augmentation is often necessary for esthetic or functional reasons. As an alternative to synthetic and xenogeneic materials, autologous fat grafting (AFG) based on liposuction is gaining popularity, yet successful transplantation and long-term volume maintenance are difficult. Standard tumescent solution formulations neglect adipocyte and stromal vascular fraction (SVF) cell survival during extraction, as well as SVF differentiation into adipocytes thereafter, all of which are crucial for the success of AFG. Here we hypothesized that addition of ascorbic acid (AA) to the tumescent solution could prevent liposuction-induced cell damage. MATERIALS AND METHODS: The effect of 0.1 mmol/L AA in tumescent solution was investigated in a previously described ex vivo model of AFG. Briefly, excision fat was infiltrated with tumescent solution, with or without AA, and incubated for 20 minutes at 37°C. Hand-assisted liposuction was then performed with a blunt cannula. Total cell viability, clonogenicity, and differentiation capacity of the SVF cells were assessed. RESULTS: With AA, 10.3% more cells and in particular 14.9% more adipocytes survived liposuction. Clonogenicity, adipocyte and osteoblast differentiation by SVF cells remained unchanged. CONCLUSIONS: Addition of AA successfully improved survival of adipocytes during liposuction without affecting SVF growth and differentiation. This study therefore identified a useful supplement to the tumescent solution which may lead to improving AFG success.

Regeneration of nerve crush injury using adipose-derived stem cells: A multimodal comparison.

INTRODUCTION: To restore full function following nerve crush injuries is critical but challenging. In an attempt to develop a viable therapy, we evaluated the effect of rat adipose-derived stem cells (rASC) in 2 different settings of a sciatic crush injury model. METHODS: In the first group, after 14 days of nerve crush injury, rASCs were injected distal to the lesion under ultrasound guidance. In the other group, alleviation of compression through clip removal (CR) was combined with epineural injection of rASCs. Gait analyses, MRI, gastrocnemius muscle weight ratio (MWR), and histomorphometry were performed for outcome analysis. RESULTS: CR combined with rASC injection resulted in less muscle atrophy, as evidenced by MWR. These findings are further supported by better functional and anatomical outcomes. DISCUSSION: Animals treated with CR and epineural stem cell injection showed enhanced anatomical and functional recovery. Muscle Nerve 58: 566-572, 2018.

Extending the limits of the anterior tibial artery as the recipient vessel for around the knee and proximal lower extremity defect reconstruction using the free anterolateral thigh and gracilis flap.

PURPOSE: The aim is to describe a technique with orthograde dissection of the anterior tibial artery (ATA) used as the recipient vessel for the end-to-end (ETE) anastomosis in defect reconstruction around the knee and for proximal/middle third leg defects with free anterolateral thigh (ALT) and gracilis flaps. PATIENTS AND METHODS: Between March 2009 and May 2014, 22 patients undergoing lower extremity reconstruction were evaluated. Of those, 4 patients were included. The locations of injury were 3 defects around the knee and 1 defect at the proximal and middle third of the lower leg (mean defect size 18 x 8.5 cm and a range of 17-20 x 5-10 cm). There were 2 cases after trauma and 2 cases with infection. Two free gracilis and 2 free ALT flaps were performed of equal size to the defects. The mean flap pedicle length was 11 cm (range of 7-16 cm) and the mean length of the mobilized recipient vessels was 10.5 cm (range of 6-14 cm). RESULTS: One flap loss (ALT) occurred, requiring a salvage procedure with a latissimus dorsi flap, whereas wound dehiscence at the donor site and a hematoma below the ALT flap was observed in 2 cases, requiring small revision. After a mean follow-up of 52 months (range of 38-87 months), there was stable soft tissue coverage in all patients. CONCLUSION: By orthograde dissection of the ATA, an adequate vessel length and size may be achieved, improving arc of rotation to successfully cover more distant defects.

From Bedside to Bench: The Effect of Muscular Denervation on Fat Grafting to the Breast by Comparing Take Rate, Quality, and Longevity.

BACKGROUND: Autologous fat grafting (AFG) to the breast is a frequent procedure in aesthetic and reconstructive surgery. Despite pure volume gain, questions remain regarding the engraftment rate, quality, and longevity. Little is known about the role of recipient tissue or innervation of the grafted area. OBJECTIVES: The goal of this study was to determine the optimal recipient layer and muscular pretreatment of AFG. METHODS: Fat was grafted to the breast, pectoralis muscle, or adjacent subcutaneous tissue of 42 rats. Nerve treatment included excision of a nerve segment, botulinum toxin (BTX) injection, or no treatment. Magnetic resonance imaging (MRI) and histological workup were carried out after 2 and 6 weeks. RESULTS: Six weeks after AFG, the proportion of viable fat cells within the grafted fat stayed high (median, [IQR]: 81% [72% to 85%]). The signs of inflammation decreased over time. Intramuscular grafting with intact nerves had a decreasing effect on the viability of the grafted cells compared with subcutaneous treatment (-10.21%; 95% confidence interval [-21.1 to 0.68]). CONCLUSIONS: If utilized on an intact nerve, intramuscular injection may lead to inferior results. If the nerve was cut or treated with BTX; however, intramuscular injection tends to be superior. These findings may prove interesting for future studies and eventual clinical application.

Evaluation of the Neo-umbilicus Cutaneous Sensitivity Following Abdominoplasty.

BACKGROUND: Abdominal cutaneous sensitivity loss after abdominoplasty is an undesirable outcome. However, little is known in the literature about sensitivity changes of the neo-umbilicus after abdominoplasty. The aim of this study was to evaluate post-abdominoplasty cutaneous sensitivity of the neo-umbilicus using clinical, quantitative, and reproducible methods. METHODS: Patients who underwent abdominoplasty were included, whereas the control group consisted of healthy volunteers with similar demographic characteristics but who did not undergo abdominoplasty. The umbilicus was divided into five zones, and superficial tactile sensitivity and spatial orientation were assessed subjectively (score 1-4) and objectively (Semmes-Weinstein monofilament examination). RESULTS: Twenty patients (45 ± 12 years) operated on consecutively between April 2012 and May 2016 and 14 healthy volunteers in the control group (39 ± 9 years) could be included. Although there were statistically significant differences (p = 0.0005) in the average cutaneous pressure thresholds between the control group (0.4 g/mm2, range 0.07-2 g/mm2) and the study group (0.4 g/mm2, range 0.07-4 g/mm2), patient satisfaction after a mean follow-up of 33 ± 16 months (range 10-62 months) was acceptable (mean satisfaction score 1.8 ± 0.7). Furthermore, spatial perceptions were precise in all patients and similar to the control group. CONCLUSION: Our long-term results indicate that spontaneous reinnervation of the neo-umbilicus after abdominoplasty together with accurate spatial orientation can occur. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Nipple Reconstruction After Autologous or Expander Breast Reconstruction: A Multimodal and 3-Dimensional Analysis.

BACKGROUND: Little is known about the influence of the underlying tissue as donor for nipple-areola complex (NAC) reconstruction. Also, there is a complete lack of knowledge about the fate of nipple volume. OBJECTIVES: The goal of this retrospective, single-institution study was to analyze a case series after nipple reconstruction using a multimodal evaluation including 3-dimensional (3D) laser scanner analyses. METHODS: Unilateral mastectomy patients after either expander-based or autologous breast reconstruction using the skate flap were included. NAC caliper measurement of nipple and areola size was performed. 3D laser scanner analysis (Minolta Vivid 900) was used to calculate nipple volume, measurement of nipple, and areolar projection and diameter. Sensitivity was evaluated using the Semmes Weinstein test and patient satisfaction by a visual analog scale (VAS 1-10). RESULTS: A total of 10 patients were included in the expander group and 12 patients were included in the flap group. After a median follow-up period of 32 months in the expander group and 34 months in the flap group, non-contact 3D laser surface scanning revealed a difference in projection of 55 to 60% compared to the contralateral side. The contraction in all 3 dimensions led to a dramatic difference in nipple volume with 12 ± 8% (flap reconstructions) and 12 ± 7% (expander reconstructions). Sensitivity of the areola showed better values after expander-based reconstruction. Despite the significant discrepancy in nipple volume and projection as well as areolar diameter, overall patient satisfaction was acceptable (VAS 4.1 ± 3.5). CONCLUSIONS: Volume assessment revealed a massive asymmetry to the intact nipple but not between expander and flap reconstructions. Although asymmetry of the areola and nipple remains, patient satisfaction is acceptable. LEVEL OF EVIDENCE 4.

Gluteal Augmentation Techniques: A Comprehensive Literature Review.

Background: Many studies of gluteal augmentation techniques have been published in recent decades, including case reports, retrospective and prospective case series, and multicenter survey reviews. However, to date, there has been no study of the overall complications or satisfaction rates associated with the broad spectrum of techniques. Objectives: The authors performed a comprehensive literature review to determine outcomes and complications of gluteoplasty techniques, including patient satisfaction. Methods: A search on PubMed/Medline was performed for clinical studies involving gluteal augmentation techniques. A priori criteria were used to review the resulting articles. Results: Fifty-two studies, published from 1969 through 2015, were included - representing 7834 treated patients. Five gluteal augmentation techniques were identified from these studies: gluteal augmentation with implants (n = 4781), autologous fat grafting (n = 2609), local flaps (n = 369), hyaluronic acid gel injection (n = 69), and local tissue rearrangement (n = 6). The overall complication rates of the most commonly utilized techniques were: 30.5% for gluteal augmentation with implants, 10.5% for autologous fat grafting, and 22% for local flaps. Patients' satisfaction was reported as consistently high for all the five techniques. Conclusions: Implant-based gluteal augmentation is associated with high patients' satisfaction despite a high complication rate, while autologous fat grafting is associated with the lowest complication rate yet including serious major complications such as fat embolism. Local flaps and local tissue rearrangements are the ideal procedures in case of massive weight loss patients. A paucity of data is available for hyaluronic acid gel injections, which appear to be effective but temporary and expensive.

Adipose-Derived Stromal Cells from Lipomas: Isolation, Characterisation and Review of the Literature.

OBJECTIVE: The aim of this study was to characterize adipose-derived stromal cells (ADSCs) from patients diagnosed with multiple symmetric lipomatosis (MSL) in order to obtain potentially new insights into the pathophysiology, pathogenesis and treatment of this disease. METHODS: Cells from the stromal vascular fraction were analysed by the colony-forming efficiency assay and flow cytometry using standard markers. Moreover, the power of adipogenic plasticity was evaluated. Finally, a literature review was performed from 1982 to 2015 using the US National Institutes of Health's PubMed database. RESULTS: Three European-descent patients diagnosed with either MSL type I or II could be identified for analysis. The resulting mean colony-forming efficiency assay was 14.3 ± 5%. Flow-cytometric analysis of the ADSCs revealed high levels of CD34 (70 ± 9%), CD45 (37 ± 13%) and CD73 (55.8 ± 14%), whereas low levels of CD31 (16.8 ± 14%) and CD105 (5.8 ± 0.7%) were detected. Furthermore, ADSCs showed a strong adipogenic potential, which is in line with the literature review. The stem cell pool in lipoma shows several alterations in biological activities, such as proliferation, apoptosis and stemness. CONCLUSIONS: ADSCs from lipoma may be interesting in the application of regenerative medicine. We discuss possible molecular treatment options to regulate their activities at the source of the MSL.

Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model.

BACKGROUND: Lymphedema is an underdiagnosed pathology which in industrialized countries mainly affects cancer patients that underwent lymph node dissection and/or radiation. Currently no effective therapy is available so that patients' life quality is compromised by swellings of the concerned body region. This unfortunate condition is associated with body imbalance and subsequent osteochondral deformations and impaired function as well as with an increased risk of potentially life threatening soft tissue infections. METHODS: The effects of PRP and ASC on angiogenesis (anti-CD31 staining), microcirculation (Laser Doppler Imaging), lymphangiogenesis (anti-LYVE1 staining), microvascular architecture (corrosion casting) and wound healing (digital planimetry) are studied in a murine tail lymphedema model. RESULTS: Wounds treated by PRP and ASC healed faster and showed a significantly increased epithelialization mainly from the proximal wound margin. The application of PRP induced a significantly increased lymphangiogenesis while the application of ASC did not induce any significant change in this regard. CONCLUSIONS: PRP and ASC affect lymphangiogenesis and lymphedema development and might represent a promising approach to improve regeneration of lymphatic vessels, restore disrupted lymphatic circulation and treat or prevent lymphedema alone or in combination with currently available lymphedema therapies.