Pluripotent cells represent a powerful tool for tissue regeneration, but their clinical utility is limited by their propensity to form teratomas. Little is known about their interaction with the surrounding niche following implantation and how this may be applied to promote survival and functional engraftment. In this study, we evaluated the ability of an osteogenic microniche consisting of a hydroxyapatite-coated, bone morphogenetic protein-2–releasing poly- l -lactic acid scaffold placed within the context of a macroenvironmental skeletal defect to guide in vivo differentiation of both embryonic and induced pluripotent stem cells. In this setting, we found de novo bone formation and participation by implanted cells in skeletal regeneration without the formation of a teratoma. This finding suggests that local cues from both the implanted scaffold/cell micro- and surrounding macroniche may act in concert to promote cellular survival and the in vivo acquisition of a terminal cell fate, thereby allowing for functional engraftment of pluripotent cells into regenerating tissue.
Angiogenesis is essential to wound repair, and vascular endothelial growth factor (VEGF) is a potent factor to stimulate angiogenesis. Here, we examine the potential of VEGF-overexpressing adipose-derived stromal cells (ASCs) for accelerating wound healing using nonviral, biodegradable polymeric vectors. Mouse ASCs were transfected with DNA plasmid encoding VEGF or green fluorescent protein (GFP) using biodegradable poly (β-amino) esters (PBAE). Cells transfected using Lipofectamine 2000, a commercially available transfection reagent, were included as controls. ASCs transfected using PBAEs showed enhanced transfection efficiency and 12-15-fold higher VEGF production compared with cells transfected using Lipofectamine 2000 (*P < 0.05). When transplanted into a mouse wild-type excisional wound model, VEGF-overexpressing ASCs led to significantly accelerated wound healing, with full wound closure observed at 8 days compared to 10-12 days in groups treated with ASCs alone or saline control (*P < 0.05). Histology and polarized microscopy showed increased collagen deposition and more mature collagen fibers in the dermis of wound beds treated using PBAE/VEGF-modified ASCs than ASCs alone. Our results demonstrate the efficacy of using nonviral-engineered ASCs to accelerate wound healing, which may provide an alternative therapy for treating many diseases in which wound healing is impaired.
Background. In the era of coronavirus disease 2019 (COVID-19), many Complex General Surgical Oncology (CGSO) fellowship programs implemented virtual interviews (VI) during the 2020 interview season. At our institution, we had the unique opportunity to conduct an inperson interview (IPI) prior to the pandemic-related travel restrictions, and a VI after the restrictions were in place. Objective. The goal of this study was to understand how the VI model compares with the traditional IPI approach. Methods. Online surveys were distributed to both groups, collecting feedback on their interview experience. Responses were evaluated using a two-sample t test assuming equal variances. Results. Twenty-three of 26 (88%) applicants completed the survey. Most applicants reported that the interview gave them a satisfactory understanding of the CGSO fellowship (100% IPI, 92% VI) and the majority in both groups felt that the interview experience allowed them to accurately represent themselves (92% and 82%, respectively). All participants in the IPI group felt they were able to get an adequate understanding of the culture of the program, while only 64% in the VI group agreed with that statement (p = 0.02). IPI applicants were more likely to
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