Mesenchymal Stem Cell-Derived Extracellular Vesicles as Proposed Therapy in a Rat Model of Cerebral Small Vessel Disease.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been employed in the past decade as therapeutic agents in various diseases, including central nervous system (CNS) disorders. We currently aimed to use MSC-EVs as potential treatment for cerebral small vessel disease (CSVD), a complex disorder with a variety of manifestations. MSC-EVs were intranasally administrated to salt-sensitive hypertension prone SBH/y rats that were DOCA-salt loaded (SBH/y-DS), which we have previously shown is a model of CSVD. MSC-EVs accumulated within brain lesion sites of SBH/y-DS. An in vitro model of an inflammatory environment in the brain demonstrated anti-inflammatory properties of MSC-EVs. Following in vivo MSC-EV treatment, gene set enrichment analysis (GSEA) of SBH/y-DS cortices revealed downregulation of immune system response-related gene sets. In addition, MSC-EVs downregulated gene sets related to apoptosis, wound healing and coagulation, and upregulated gene sets associated with synaptic signaling and cognition. While no specific gene was markedly altered upon treatment, the synergistic effect of all gene alternations was sufficient to increase animal survival and improve the neurological state of affected SBH/y-DS rats. Our data suggest MSC-EVs act as microenvironment modulators, through various molecular pathways. We conclude that MSC-EVs may serve as beneficial therapeutic measure for multifactorial disorders, such as CSVD.

[SCARPA FASCIA AND ABDOMINAL WALL DEEP ADIPOSE COMPARTMENT PRESERVATION IN ABDOMINOPLASTY - CURRENT CLINICAL AND ANATOMICAL REVIEW].

INTRODUCTION: During the last two decades, in parallel to the increased prevalence of bariatric procedures, there has been a marked increase in the prevalence of abdominoplasty surgery in the United States, and in accordance an increase in the scientific and clinical research related to all aspects of this technique. The most common complication of abdominoplasty is the formation of post-operative seroma. Various theories have been raised regarding the pathophysiology of seroma formation, and numerous methods for seroma prevention have been employed and tested. In the early 90's, a new theory argued that post-operative seroma formation is secondary to damage caused to the abdominal wall's lymphatic drainage during flap undermining. In light of this theory, a new surgical technique was suggested to execute the flap undermining in a more superficial plane. This enabled the preservation of the scarpa fascia and the deep adipose compartment, which preserved the integrity of the abdominal wall lymphatic collectors. This method was successful in reducing the rate of postoperative seroma formation. Recent studies have shed new light on the anatomy of the abdominal lymphatic collectors, pathophysiology of seroma formation and methods of its prevention. This new data undermines the foundations of the scarpa fascia preservation theory, and the surgical technique that was derived from it. A new theory that tries to settle the contradiction between the clinical success of the technique in reducing seromas and the new findings regarding abdominal wall's lymphatic collectors anatomy, is the presence of a 'sticky interface' between the deep adipose compartment and the flap.

Medical Students' Knowledge of Plastic Surgery as a Reflection of the Public Perception.

Plastic surgery is a broad field that requires a mixed skillset. Therefore, it is important that students be exposed to all its various subspecialties to make informed career decisions and to properly refer patients in different clinical situations. A nationwide survey was conducted of Israeli medical students to investigate their knowledge and perceptions regarding the field of plastic surgery and its subspecialties, and the impact of a clinical rotation in plastic surgery on these factors. A total of 300 subjects responded. Approximately, 61% of the cohort was female and 70% were enrolled in a 6-year program. About one-third stated that their field of interest was surgical rather than medical. Significant variability was noted in the accuracy of responses to questions about different procedures encompassed in the scope of plastic surgery. Although 90% of the students were aware of some common plastic surgery procedures that are also often thought to be well known to the public, only 50% were able to correctly identify lesser-known surgeries performed by plastic surgeons. Knowledge about plastic surgery was unrelated to an interest in the field. We recommend adjusting preclinical instruction and clinical rotations in plastic surgery to better prepare students to select a specialty best suited to their future goals, as well as to improve their ability to refer patients to other specialists as necessary.

Cancer-Associated Fibroblasts in Mycosis Fungoides Promote Tumor Cell Migration and Drug Resistance through CXCL12/CXCR4.

Cancer cells are known to reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs) to act as tumor supporters. The presence and role of CAFs in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, are unknown. This study sought to characterize CAFs in MF and their cross talk with the lymphoma cells using primary fibroblast cultures from punch biopsies of patients with early-stage MF and healthy subjects. MF cultures yielded significantly increased levels of FAPα, a CAF marker, and CAF-associated genes and proteins: CXCL12 (ligand of CXCR4 expressed on MF cells), collagen XI, and matrix metalloproteinase 2. Cultured MF fibroblasts showed greater proliferation than normal fibroblasts in ex vivo experiments. A coculture with MyLa cells (MF cell line) increased normal fibroblast growth, reduced the sensitivity of MyLa cells to doxorubicin, and enhanced their migration. Inhibiting the CXCL12/CXCR4 axis increased doxorubicin-induced apoptosis of MyLa cells and reduced MyLa cell motility. Our data suggest that the fibroblasts in MF lesions are more proliferative than fibroblasts in normal skin and that CAFs protect MF cells from doxorubicin-induced cell death and increase their migration through the secretion of CXCL12. Reversing the CAF-mediated tumor microenvironment in MF may improve the efficiency of anticancer therapy.