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Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line–derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and g-ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 μm2) compared to autograft (4.62 ± 3.99 μm2) and PCL/Empty (4.52 ± 5.16 μm2) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.

Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve 58: 251-260, 2018.

BackgroundVascularized composite allotransplantation opens new possibilities in reconstructive transplantation such as hand or face transplants. Lifelong immunosuppression and its side-effects are the main drawbacks of this procedure. Mesenchymal stem cells (MSCs) have clinically useful immunomodulatory effects and may be able to reduce the burden of chronic immunosuppression. Herein, we assess and compare characteristics and immunomodulatory capacities of bone marrow- and adipose tissue-derived MSCs isolated from the same human individual across defined human leukocyte antigen (HLA) barriers.Materials and methodsSamples of omental (o.) adipose tissue, subcutaneous (s.c.) adipose tissue, and bone marrow aspirate from 10 human organ donors were retrieved and MSCs isolated. Cells were characterized by flow cytometry and differentiated in three lineages: adipogenic, osteogenic, and chondrogenic. In mixed lymphocyte reactions, the ability of adipose-derived mesenchymal stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (BMSCs) to suppress the immune response was assessed and compared within individual donors. HLA mismatched or mitogen stimulations were analyzed in co-culture with different MSC concentrations. Supernatants were analyzed for cytokine contents.ResultsAll cell types, s.c.ASC, o.ASC, and BMSC demonstrated individual differentiation potential and cell surface markers. Immunomodulating effects were dependent on dose and cell passage. Proliferation of responder cells was most effectively suppressed by s.c.ASCs and combination with BMSC resulted in highly efficient immunomodulation. Immunomodulation was not cell contact-dependent and cells demonstrated a specific cytokine secretion.ConclusionWhen human ASCs and BMSCs are isolated from the same individual, both show effective immunomodulation across defined HLA barriers in vitro. We demonstrate a synergistic effect when cells from the same biologic system were combined. This cell contact-independent function underlines the potential of clinical systemic application of MSCs.

Schools are often unsafe for lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) students; they frequently experience negative or hostile school climates, including bullying and discrimination based on sexual orientation and gender identity at school. Negative school climates and discriminatory experiences can threaten LGBTQ students’ well-being. Simultaneously, a consistent body of research identifies strategies to support LGBTQ and all students to be safe and thrive at school. First, policies that specifically identify or enumerate protected groups such as LGBTQ students create supportive contexts for all youth. Second, professional development prepares educators and other school personnel with tools to support and protect all students. Third, access to information and support related to sexual orientation and gender identity or expression (SOGIE), including curricula that is SOGIE-inclusive, provides students with resources, support, and inclusion, creating school climate. Fourth, the presence of student-led clubs or organizations such as gender-sexuality alliances (i.e., GSAs) improve students’ school experiences and well-being, and contribute to positive school climate. This article reviews the research foundations of each of these strategies and concludes with recommendations for multiple audiences: policymakers, school personnel, parents, and students.

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Background Laxity of the submental area is a common cosmetic complaint of the aging population. Objectives The objective was to determine the safety and effectiveness of a temperature-controlled minimally invasive percutaneous monopolar radiofrequency device to improve dermal laxity and achieve lift. Methods A total of 72 subjects (35–65 years old) with mild to moderate skin laxity in the submental area were included in this single-center prospective study (New Jersey, USA). All subjects received one treatment at baseline with an average subdermal temperature of 63°C. The primary endpoint was the proportion of subjects with at least a 20 mm 2 decrease in surface area at Day 90 based on 3D photography. Secondary endpoints included skin elasticity measured by a cutometer, assessment by a blinded physician panel using 2D photographs, and physician and subject-reported outcomes. Results At Day 90, 72.1% (95% confidence interval: 62.2-84.0%, P < 0.001) of subjects achieved at least a 20 mm 2 lift of the submental area. All values for skin elasticity (R2, R5, R7) showed significant improvement by 180 days as measured by cutometer. 74.2% of subjects were graded by the independent panel as “Improved” at 90 days. (62.0-84.2%, P<0.001). The treatment was well tolerated, and only one possibly related serious adverse event was reported (pharyngeal inflammation). Conclusions Treatment with temperature-controlled monopolar radiofrequency alone is a safe and effective treatment to achieve submental lift for at least six months.

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