BackgroundThe therapeutic efficacy of adipose-derived stem cells (ASCs) has been investigated for numerous clinical indications, including autoimmune and neurodegenerative diseases. Less is known using the crude adipose product called stromal vascular fraction (SVF) as therapy, although our previous studies demonstrated greater efficacy at late-stage disease compared to ASCs in the experimental autoimmune encephalomyelitis (EAE) mouse, a model of multiple sclerosis. In this study, SVF cells and ASCs were administered during the pathogenic progression, designated as early disease, to elucidate immunomodulatory mechanisms when high immune cell activities associated with autoimmune signaling occur. These implications are essential for clinical translation when considering timing of administration for cell therapies.MethodsWe investigated the effects of SVF cells and ASCs by analyzing the spleens, peripheral blood, and central nervous system tissues throughout the course of EAE disease following administration of SVF cells, ASCs, or vehicle. In vitro, immunomodulatory potentials of SVF cells and ASCs were measured when exposed to EAE-derived splenocytes.ResultsInterestingly, treatment with SVF cells and ASCs transiently enhanced the severity of disease directly after administration, substantiating this critical immunomodulatory signaling. More importantly, it was only the EAE mice treated with SVF cells that were able to overcome the advancing pathogenesis and showed improvements by the end of the study. The frequency of lesions in spinal cords following SVF treatment correlated with diminished activities of the T helper type 1 cells, known effector cells of this disease. Co-cultures with splenocytes isolated from EAE mice revealed transcripts of interleukin-10 and transforming growth factor-β, known promoters of regulatory T cells, that were greatly expressed in SVF cells compared to ASCs, and expression levels of signaling mediators related to effector T cells were insignificant in both SVF cells and ASCs.ConclusionThis is the first evidence, to date, to elucidate a mechanism of action of SVF treatment in an inflammatory, autoimmune disease. Our data supports key immunomodulatory signaling between cell therapies and T cells in this T cell-mediated disease. Together, treatment with SVF mediated immunomodulatory effects that diminished effector cell activities, promoted regulatory T cells, and reduced neuroinflammation.
Objectives: Prophylactic flexible bronchoscopy immediately following open airway reconstruction allows for directed clearance of the distal airways, potentially reducing the rate of certain postoperative respiratory complications. In this investigation, we sought to determine if prophylactic flexible bronchoscopy at the conclusion of pediatric open airway reconstruction has any benefit over blind flexible suctioning of the trachea. Methods: A retrospective, single-center study at an urban tertiary care hospital was completed. From January 2010 to April 2013, patients underwent open airway reconstruction, immediately followed by blind flexible suctioning of the trachea for distal airway clearance. From May 2013 through December 2016, sequential patients underwent prophylactic flexible bronchoscopy immediately following airway reconstruction. Results: A total of 29 patients (age: 3.6 months-6.2 years) met inclusion criteria. Sixteen sequential patients underwent simple blind flexible suctioning and 13 sequential patients underwent directed, prophylactic flexible bronchoscopy. Demographics and comorbidities between the groups were equivalent other than slightly older age in the prophylactic bronchoscopy group. All clinical outcomes analyzed were equivalent other than faster time to room air ( P < .002) and a decrease in the number of chest physical therapy sessions ( P < .02) in a subset of patients who did not undergo prophylactic bronchoscopy. Conclusion: This investigation suggests that the use of prophylactic flexible bronchoscopy immediately following open airway reconstruction may not be superior to blind flexible suctioning of the trachea in limiting postoperative pulmonary complications. Further studies of greater power are needed to better elucidate any small differences that may exist between these two interventions.
A full-term, 7-month-old male infant presented to an outpatient pediatric otolaryngology clinic with a firm, irregularly shaped posterior neck mass. He had been diagnosed prenatally with cerebellar hypoplasia, so a magnetic resonance imaging study of the brain was performed at 1 month of age. This study demonstrated an incidental solid, homogenous mass in the subcutaneous fat of the right occiput with irregular borders and infiltration into the paraspinal musculature (Figure , A). On examination, the upper posterior neck mass was deep to palpation without overlying skin changes. The patient had no discomfort, and neck movement was not restricted.At 7 months of age, the patient underwent ultrasonography to assess interval change of the lesion, which confirmed a 3.4-cm × 1.6-cm × 3.7-cm mass that had grown proportionally with the patient and was relatively avascular. Shortly thereafter, the mass was excised en bloc along with a cuff of adjacent posterior neck muscle and subcutaneous tissue. Grossly, the lesion was firm, round, and white in color with a smooth intact border but no discrete capsule. Histologic examination revealed cells with oval nuclei and multiple small nucleoli surrounded by a pale eosinophilic and slightly fibrillary stroma (Figure, B and C). Immunohistochemical studies were diffusely positive for glial fibrillary acidic protein and vimentin, and focally positive for S100, NeuN, and synaptophysin.
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