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BACKGROUND: Total parotidectomy with facial nerve sacrifice creates 2 challenging reconstructive problems: restoration of facial contour and facial nerve rehabilitation. Strong evidence suggesting that vascularized nerve grafts are superior to nonvascularized nerve grafts motivated our team to develop a chimeric scapulodorsal flap combining the usual harvestable local tissues with the vascularized latissimus dorsi motor nerve (SD-LDVxN). We present our experiences developing a new program at University of California, San Diego, highlighting our first case here, and present preliminary retrospective results focusing on the functional outcomes of facial nerve reanimation. MATERIALS AND METHODS: The first case performed in the United States was a 57-year-old woman with stage IVA left parotid adenoid cystic carcinoma and House-Brackmann grade 6 facial palsy. She underwent total parotidectomy with facial nerve sacrifice and a free chimeric SD-LDVxN flap reconstruction. She had an unremarkable postoperative course, and 3- and 6-month follow-up functional results are reported. Preliminary functional results from our total series of 25 patients were reported. RESULTS: At her 3-month follow-up, she was a House-Brackmann 5 with a static eFACE score of 37, dynamic eFACE score of 31, and smile eFACE score of 48. At her 6-month follow-up, she was a House-Brackmann 5 with a static eFACE score of 50, dynamic eFACE score of 27, and smile eFACE score of 53. Preliminary results from our total series of 25 patients with an average of 5 years of follow-up were a House-Brackmann 2.5 and eFACE scores of 83.1 for static facial symmetry, 67.5 for dynamic facial symmetry, and 77.7 for smile score. Twenty of the 25 patients had postoperative radiotherapy. No local tumor recurrence had been reported. The average reinnervation time was 9 months and ranged from 3 to 15 months. CONCLUSIONS: The SD-LDVxN flap is a highly resourceful solution to reconstruct complex parotid defects, especially those that sacrifice the facial nerve. The vascularized nerve graft allows for primary facial reanimation. Nerve recovery may be superior to what could be expected with a conventional nerve graft.
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Parálisis Facial , Neoplasias de la Parótida , Procedimientos de Cirugía Plástica , Músculos Superficiales de la Espalda , Nervio Facial/cirugía , Parálisis Facial/cirugía , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Parótida/cirugía , Estudios Retrospectivos , Colgajos QuirúrgicosRESUMEN
OBJECTIVE: This review details the agents for fluorescence-guided nerve imaging in both preclinical and clinical use to identify factors important in selecting nerve-specific fluorescent agents for surgical procedures. BACKGROUND: Iatrogenic nerve injury remains a significant cause of morbidity in patients undergoing surgical procedures. Current real-time identification of nerves during surgery involves neurophysiologic nerve stimulation, which has practical limitations. Intraoperative fluorescence-guided imaging provides a complimentary means of differentiating tissue types and pathology. Recent advances in fluorescence-guided nerve imaging have shown promise, but the ideal agent remains elusive. METHODS: In February 2018, PubMed was searched for articles investigating peripheral nerve fluorescence. Key terms used in this search include: "intraoperative, nerve, fluorescence, peripheral nerve, visualization, near infrared, and myelin." Limits were set to exclude articles exclusively dealing with central nervous system targets or written in languages other than English. References were cross-checked for articles not otherwise identified. RESULTS: Of the nonspecific agents, tracers that rely on axonal transport showed the greatest tissue specificity; however, neurovascular dyes already enjoy wide clinical use. Fluorophores specific to nerve moieties result in excellent nerve to background ratios. Although noteworthy findings on tissue specificity, toxicity, and route of administration specific to each fluorescent agent were reported, significant data objectively quantifying nerve-specific fluorescence and toxicity are lacking. CONCLUSIONS: Fluorescence-based nerve enhancement has advanced rapidly over the past 10 years with potential for continued utilization and progression in translational research. An ideal agent would be easily administered perioperatively, would not cross the blood-brain barrier, and would fluoresce in the near-infrared spectrum. Agents administered systemically that target nerve-specific moieties have shown the greatest promise. Based on the heterogeneity of published studies and methods for reporting outcomes, it appears that the development of an optimal nerve imaging agent remains challenging.
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Cuidados Intraoperatorios/métodos , Imagen Óptica/métodos , Nervios Periféricos/diagnóstico por imagen , Medios de Contraste , Colorantes Fluorescentes , Humanos , Especificidad de Órganos , Sensibilidad y EspecificidadRESUMEN
Target-blind activity-based screening of molecular libraries is often used to develop first-generation compounds, but subsequent target identification is rate-limiting to developing improved agents with higher specific affinity and lower off-target binding. A fluorescently labeled nerve-binding peptide, NP41, selected by phage display, highlights peripheral nerves in vivo. Nerve highlighting has the potential to improve surgical outcomes by facilitating intraoperative nerve identification, reducing accidental nerve transection, and facilitating repair of damaged nerves. To enable screening of molecular target-specific molecules for higher nerve contrast and to identify potential toxicities, NP41's binding target was sought. Laminin-421 and -211 were identified by proximity-based labeling using singlet oxygen and by an adapted version of TRICEPS-based ligand-receptor capture to identify glycoprotein receptors via ligand cross-linking. In proximity labeling, photooxidation of a ligand-conjugated singlet oxygen generator is coupled to chemical labeling of locally oxidized residues. Photooxidation of methylene blue-NP41-bound nerves, followed by biotin hydrazide labeling and purification, resulted in light-induced enrichment of laminin subunits α4 and α2, nidogen 1, and decorin (FDR-adjusted P value < 10-7) and minor enrichment of laminin-γ1 and collagens I and VI. Glycoprotein receptor capture also identified laminin-α4 and -γ1. Laminins colocalized with NP41 within nerve sheath, particularly perineurium, where laminin-421 is predominant. Binding assays with phage expressing NP41 confirmed binding to purified laminin-421, laminin-211, and laminin-α4. Affinity for these extracellular matrix proteins explains the striking ability of NP41 to highlight degenerated nerve "ghosts" months posttransection that are invisible to the unaided eye but retain hollow laminin-rich tubular structures.
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The growing concern over the toxicity of Gd-based contrast agents used in magnetic resonance imaging (MRI) motivates the search for less toxic and more effective alternatives. Among these alternatives, iron-iron oxide (Fe@FeOx) core-shell architectures have been long recognized as promising MRI contrast agents while limited information on their engineering is available. Here we report the synthesis of 10 nm large Fe@FeOx nanoparticles, their coating with a 11 nm thick layer of dense silica and functionalization by 5 kDa PEG chains to improve their biocompatibility. The nanomaterials obtained have been characterized by a set of complementary techniques such as infra-red and nuclear magnetic resonance spectroscopies, transmission electron microscopy, dynamic light scattering and zetametry, and magnetometry. They display hydrodynamic diameters in the 100 nm range, zetapotential values around -30 mV, and magnetization values higher than the reference contrast agent RESOVIST®. They display no cytotoxicity against 1BR3G and HCT116 cell lines and no hemolytic activity against human red blood cells. Their nuclear magnetic relaxation dispersion (NMRD) profiles are typical for nanomaterials of this size and magnetization. They display high r2 relaxivity values and low r1 leading to enhanced r2/r1 ratios in comparison with RESOVIST®. All these data make them promising contrast agents to detect early stage tumors.
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Dextranos/química , Compuestos Férricos/química , Hierro/química , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Dióxido de Silicio , Línea Celular Tumoral , Materiales Biocompatibles Revestidos , Humanos , Nanopartículas de Magnetita/ultraestructura , Modelos Teóricos , Dióxido de Silicio/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Engineered nerve guidance conduits (NGCs) have been demonstrated for repairing peripheral nerve injuries. However, there remains a need for an advanced biofabrication system to build NGCs with complex architectures, tunable material properties, and customizable geometrical control. Here, a rapid continuous 3D-printing platform was developed to print customizable NGCs with unprecedented resolution, speed, flexibility, and scalability. A variety of NGC designs varying in complexity and size were created including a life-size biomimetic branched human facial NGC. In vivo implantation of NGCs with microchannels into complete sciatic nerve transections of mouse models demonstrated the effective directional guidance of regenerating sciatic nerves via branching into the microchannels and extending toward the distal end of the injury site. Histological staining and immunostaining further confirmed the progressive directional nerve regeneration and branching behavior across the entire NGC length. Observational and functional tests, including the von Frey threshold test and thermal test, showed promising recovery of motor function and sensation in the ipsilateral limbs grafted with the 3D-printed NGCs.
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BACKGROUND AND OBJECTIVES: Molecularly targeted fluorescent molecules may help detect tumors that are unseen by traditional white-light surgical techniques. We sought to evaluate a fluorescent ratiometric activatable cell penetrating peptide (RACPP) for tumor detection in a transgenic model of PTC. METHODS: Thirteen BRAFV600E mice with PTC were studied-seven injected intravenously with RACPP, four controls with saline. Total thyroidectomy was performed with microscopic white-light visualization. Fluorescent imaging of post-thyroidectomy fields was performed, and tissue with increased signal was removed and evaluated for PTC. Final samples were analyzed by a pathologist blinded to conditions. Vocal cord function was evaluated postoperatively with video laryngoscopy. RESULTS: The average in situ ratiometric (Cy5/Cy7) thyroid tumor-to-background contrast ratio was 2.27 +/- 0.91. Fluorescence-guided clean-up following thyroidectomy identified additional tumor in 2 of 7 RACPP animals (smallest dimension 1.2 mm), and decreased the number of animals with residual tumor from 4 to 3. All retained tumor foci on final pathology were smaller than 0.76 mm. Intact vocal abduction was present in all of the RACPP animals. CONCLUSIONS: RACPPs successfully targeted PTC in a transgenic thyroidectomy model, and allowed for residual tumor detection that reduced positive margins beyond what was possible with white-light surgery alone.
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Carcinoma/terapia , Péptidos de Penetración Celular , Terapia Molecular Dirigida/métodos , Neoplasias de la Tiroides/terapia , Tiroidectomía , Animales , Animales Modificados Genéticamente , Carcinoma/genética , Carcinoma/fisiopatología , Carcinoma/cirugía , Carcinoma Papilar , Modelos Animales de Enfermedad , Fluorescencia , Ácido Glutámico , Laringoscopía , Laringe/fisiopatología , Ratones , Proteínas Proto-Oncogénicas B-raf/genética , Coloración y Etiquetado , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/fisiopatología , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Resultado del Tratamiento , Valina , Grabación en Video , Pliegues Vocales/fisiopatologíaRESUMEN
BACKGROUND: The aim of this study was to evaluate the efficacy of using matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9)-cleavable ratiometric activatable cell-penetrating peptides (RACPPs) conjugated to Cy5 and Cy7 fluorophores to accurately label pancreatic cancer for fluorescence-guided surgery (FGS) in an orthotopic mouse model. METHODS: Orthotopic mouse models were established using MiaPaCa-2-GFP human pancreatic cancer cells. Two weeks after implantation, tumor-bearing mice were randomized to conventional white light reflectance (WLR) surgery or FGS. FGS was performed at far-red and infrared wavelengths with a customized fluorescence-dissecting microscope 2 h after injection of MMP-2 and MMP-9-cleavable RACPPs. Green fluorescence imaging of the GFP-labeled cancer cells was used to assess the effectiveness of surgical resection and monitor recurrence. At 8 weeks, mice were sacrificed to evaluate tumor burden and metastases. RESULTS: Mice in the WLR group had larger primary tumors than mice in the FGS group at termination [1.72 g ± standard error (SE) 0.58 vs. 0.25 g ± SE 0.14; respectively, p = 0.026). Mean disease-free survival was significantly lengthened from 5.33 weeks in the WLR group to 7.38 weeks in the FGS group (p = 0.02). Recurrence rates were lower in the FGS group than in the WLR group (38 vs. 73 %; p = 0.049). This translated into lower local and distant recurrence rates for FGS compared to WLR (31 vs. 67 for local recurrence, respectively, and 25 vs. 60 % for distant recurrence, respectively). Metastatic tumor burden was significantly greater in the WLR group than in the FGS group (96.92 mm(2) ± SE 52.03 vs. 2.20 mm(2) ± SE 1.43; respectively, χ (2) = 5.455; p = 0.02). CONCLUSIONS: RACPPs can accurately and effectively label pancreatic cancer for effective FGS, resulting in better postresection outcomes than for WLR surgery.
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Péptidos de Penetración Celular/administración & dosificación , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Recurrencia Local de Neoplasia/prevención & control , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Cirugía Asistida por Computador , Animales , Péptidos de Penetración Celular/metabolismo , Femenino , Fluorescencia , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Metaloproteinasa 2 de la Matriz/química , Metaloproteinasa 9 de la Matriz/química , Ratones , Ratones Desnudos , Microscopía Fluorescente , Metástasis de la Neoplasia , Imagen Óptica/métodos , Carga TumoralRESUMEN
In this work, we report an innovative method for synthesizing BiOI nanoplate powder by a slow basification of an aqueous solution constituted of Bi(NO3)3 and KI. The basification was done with NH3 vapor which was naturally generated on top of an NH4OH solution kept in a closed space. The impact of the basification rate on the morphology and crystallinity of the BiOI product was investigated. Herein, we also report on the use of newly produced BiOI nanoplate powder together with the VO(acac)2 precursor for fabricating BiVO4 photoanodes for solar driven water splitting applications. We also discuss how the morphology of BiOI nanoplates and their orientation on a fluorine doped tin oxide substrate will affect the morphology, topology and photocatalytic performance of the electrode. The BiVO4 photoanode showed a photocatalytic current density of 0.55 mA cm-2 at 1.23 V vs. the Reversible Hydrogen Electrode (RHE) when assayed in a pH 7 phosphate buffer electrolyte and under 1 sun illumination.
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High-resolution imaging of molecules intrinsically involved in malignancy and metastasis would be of great value for clinical detection and staging of tumors. We now report in vivo visualization of matrix metalloproteinase activities by MRI and fluorescence of dendrimeric nanoparticles coated with activatable cell penetrating peptides (ACPPs), labeled with Cy5, gadolinium, or both. Uptake of such nanoparticles in tumors is 4- to 15-fold higher than for unconjugated ACPPs. With fluorescent molecules, we are able to detect residual tumor and metastases as small as 200 microm, which can be resected under fluorescence guidance and analyzed histopathologically with fluorescence microscopy. We show that uptake via this mechanism is comparable to that of other near infrared protease sensors, with the added advantage that the approach is translatable to MRI. Once activated, the Gd-labeled nanoparticles deposit high levels (30-50 microM) of Gd in tumor parenchyma with even higher amounts deposited in regions of infiltrative tumor, resulting in useful T(1) contrast lasting several days after injection. These results should improve MRI-guided clinical staging, presurgical planning, and intraoperative fluorescence-guided surgery. The approach may be generalizable to deliver radiation-sensitizing and chemotherapeutic agents.
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Colorantes Fluorescentes , Imagen por Resonancia Magnética , Nanopartículas , Neoplasias Experimentales/metabolismo , Péptido Hidrolasas/metabolismo , Péptidos/metabolismo , Animales , Espectrometría de Masas , Ratones , Ratones Desnudos , Microscopía Fluorescente , Neoplasias Experimentales/diagnósticoRESUMEN
The completeness of tumor removal during surgery is dependent on the surgeon's ability to differentiate tumor from normal tissue using subjective criteria that are not easily quantifiable. A way to objectively assess tumor margins during surgery in patients would be of great value. We have developed a method to visualize tumors during surgery using activatable cell-penetrating peptides (ACPPs), in which the fluorescently labeled, polycationic cell-penetrating peptide (CPP) is coupled via a cleavable linker to a neutralizing peptide. Upon exposure to proteases characteristic of tumor tissue, the linker is cleaved, dissociating the inhibitory peptide and allowing the CPP to bind to and enter tumor cells. In mice, xenografts stably transfected with green fluorescent protein show colocalization with the Cy5-labeled ACPPs. In the same mouse models, Cy5-labeled free ACPPs and ACPPs conjugated to dendrimers (ACPPDs) delineate the margin between tumor and adjacent tissue, resulting in improved precision of tumor resection. Surgery guided by ACPPD resulted in fewer residual cancer cells left in the animal after surgery as measured by Alu PCR. A single injection of ACPPD dually labeled with Cy5 and gadolinium chelates enabled preoperative whole-body tumor detection by MRI, intraoperative guidance by real-time fluorescence, intraoperative histological analysis of margin status by fluorescence, and postoperative MRI tumor quantification. Animals whose tumors were resected with ACPPD guidance had better long-term tumor-free survival and overall survival than animals whose tumors were resected with traditional bright-field illumination only.
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Supervivencia Celular , Neoplasias Experimentales/cirugía , Péptidos/administración & dosificación , Animales , Fluorescencia , Ratones , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Péptidos/metabolismo , Reacción en Cadena de la PolimerasaRESUMEN
In real time: thrombin activation in vivo can be imaged in real time with ratiometric activatable cell penetrating peptides (RACPPs). RACPPs are designed to combine 1) dual-emission ratioing, 2) far red to infrared wavelengths for in vivo mammalian imaging, and 3) cleavage-dependent spatial localization. The most advanced RACPP uses norleucine (Nle)-TPRSFL as a linker that increases sensitivity to thrombin by about 90-fold.
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Péptidos de Penetración Celular/metabolismo , Trombina/metabolismo , Animales , Fluorescencia , Transferencia Resonante de Energía de Fluorescencia/métodos , Ratones , Ratones TransgénicosRESUMEN
OBJECTIVE: Delayed peripheral nerve repair is complicated by nerve degeneration and atrophy that can prevent identification. We use a murine facial nerve transection model to demonstrate the efficacy of ALM-488 (bevonescein) in labeling degenerated facial nerves with quantitative image analysis and qualitative survey data. STUDY DESIGN: Prospective cohort study. SETTING: Laboratory. METHODS: Ten wild-type mice underwent transection of the lower facial nerve division with subsequent degeneration. Either 9 (n = 5 mice) or 12 (n = 5 mice) weeks later, mice underwent intravenous infusion of ALM-488 with in vivo real-time fluorescence imaging (FL) of the facial nerve. Using ImageJ, the mean gray value of each nerve segment under white light reflectance (WLR) and FL was compared to that of adjacent soft tissue to calculate the signal-to-background ratio (SBR). A survey was distributed to evaluate the perceived utility of ALM-488 in surgeon identification of degenerated nerves. RESULTS: The mean SBR of degenerated nerves was 1.08 (standard deviation [SD]: 0.07) under WLR and 2.11 (SD: 0.31) under FL (p < 0.001). In mice with degenerated nerves, survey participants identified on average 3.01 (SD: 1.84) nerve branches under WLR and 5.73 (SD: 1.88) under FL (p < 0.0001). Under FL, 47 of 48 survey responses correctly identified isolated, degenerated nerves; in contrast, only 12 responses identified degenerated nerves under WLR (p < 0.0001). CONCLUSION: Preoperative intravenous infusion of ALM-488 with FL improves the identification of degenerated facial nerves. ALM-488 also improves surgeon confidence in nerve identification, particularly in degenerated nerve branches that are not visible with WLR.
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Traumatismos del Nervio Facial , Nervio Facial , Ratones , Humanos , Animales , Nervio Facial/patología , Estudios Prospectivos , Degeneración Nerviosa/patologíaRESUMEN
Objective: Facial palsy affects patients of all backgrounds, yet no existing studies describe differences in its treatment patterns between demographic groups. Methods: We used the National Surgical Quality Improvement Project database to investigate whether race and sex disparities exist in facial reanimation surgery. Patients were identified using CPT codes corresponding to facial-nerve procedures. Results: Seven hundred sixty-one patients met criteria; 681 self-identified as White (89.5%), 51 as Black (6.7%), 43 as Hispanic (5.6%), 23 as Asian (3.0%), and 5 patients as other (0.61%). White patients were more than twice as likely to undergo brow ptosis repair than Non-White patients (OR 2.49, 95% CI 1.16-6.15, p = .03). After controlling for malignancy, men had longer operative times than women (480.2 vs. 413.9 min, p = .04) and higher likelihood of free tissue transfer (OR 4.1, 95% CI 1.9-9.8), fascial free tissue transfer (OR 10.7, 95% CI 2.1-195), and ectropion repair (OR 1.8, 95% CI 1.2-2.8). Conclusion: Most patients undergoing facial reanimation surgery in the United States are White. Men have longer operative times and a higher likelihood of undergoing free fascial grafts and cutaneous and fascial free tissue transfer than women regardless of malignancy status. Level of Evidence: 2c.
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Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells that can be isolated from bone marrow, adipose tissue, the umbilical cord, dental pulp, etc. These cells have unique properties that give them excellent therapeutic potential, including immunoregulation, immunomodulation, and tissue regeneration functions. MSC-based products are considered advanced therapy medicinal products (ATMPs) under European regulations (1394/2007); thus, they must be manufactured under good manufacturing practices and via effective manufacturing methods. The former can be achieved via a proper laboratory design and compliance with manufacturing protocols, whereas the latter requires an approach that ensures that the quality of the products is consistent regardless of the manufacturing procedure. To meet these daunting requirements, this study proposes an exchangeable approach that combines optimized and equivalent manufacturing processes under the Quality by Design (QbD) principle, allowing investigators to convert from small laboratory-scale to large-scale manufacturing of MSC-based products for clinical applications without altering the quality and quantity of the cell-based products.
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Production of hydrogen from a renewable source that is water requires the development of sustainable catalytic processes. This implies, among others, developing efficient catalytic materials from abundant and low-cost resources and investigating their performance, especially in the oxidation of water as this half-reaction is the bottleneck of the water splitting process. For this purpose, NiFe-based nanoparticles with sizes ca. 3-4 nm have been synthesized by an organometallic approach and characterized by complementary techniques (WAXS, TEM, STEM-HAADF, EDX, XPS, and ATR-FTIR). They display a Ni core and a mixed Ni-Fe oxide shell. Once deposited onto FTO electrodes, they have been assessed in the electrocatalytic oxygen evolution reaction under alkaline conditions. Three different Ni/Fe ratios (2/1, 1/1 and 1/9) have been studied in comparison with their monometallic counterparts. The Ni2Fe1 nanocatalyst displayed the lowest overpotential (320 mV at j = 10 mA cm-2) as well as excellent stability over 16 h.
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OBJECTIVE: Fluorescence-guided surgery (FGS) is a rapidly developing intraoperative technology, and many contrast agents are currently under investigation. We sought to provide a review of the current state of FGS clinical trials in Otolaryngology, emphasizing its oncologic applications. METHODS: According to the preferred reporting Items for systematic reviews and meta-analyses (PRISMA) workflow for scoping reviews, a clinical trial search was performed across multiple international clinical trials registries, searching for permutations of "fluorescence," "tumor," "surgery," and "nerve" to identify all relevant studies. Studies that were active, enrolling, or soon to be enrolling patients undergoing head and neck surgery were included. RESULTS: Nineteen studies were eligible for inclusion. Seventeen studies are focused on FGS for oncologic resection and lymph node detection. One study assesses peripheral nerve fluorescence, and one evaluates normal parathyroid function after thyroidectomy. Contrast agents under development are conjugated to fluorophores that excite in the 800 nm (indocyanine green), 410 nm (5-aminolevulinic acid), 700 nm (Cyanine 5.5), and 525 nm ranges (fluorescein derivatives). CONCLUSION: Presently, there are 19 ongoing trials investigating novel FGS contrast agents for their safety, efficacy, and utility in Otolaryngology-Head and Neck Surgery. These agents rely on unique fluorophores and absorption ranges in the near-infrared and visible light spectra. FGS studies are expanding within Otolaryngology-Head and Neck Surgery with profound implications in oncologic surgery, lymph node detection, and anatomic and functional assessment. Laryngoscope, 132:36-44, 2022.
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Ensayos Clínicos como Asunto , Colorantes Fluorescentes , Procedimientos Quirúrgicos Otorrinolaringológicos , HumanosRESUMEN
Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.
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Células Madre Mesenquimatosas , Tejido Adiposo , Diferenciación Celular/genética , Humanos , Medicina Regenerativa , Cordón UmbilicalRESUMEN
Exostoses and osteomas are benign bony lesions of the auditory canal. Although common in the external auditory canal, they are rare and difficult to distinguish in the internal auditory canal (IAC). In this literature review and case presentation, we define radiologic and histologic criteria to differentiate exostoses from osteomas of the IAC. Two patients with exostoses and 1 patient with an osteoma of the IAC are described here. Patient 1 presented with disabling vertigo and was found to have bilateral exostoses with nerve impingement on the right. After removal of the right-sided exostoses via retrosigmoid craniotomy, the patient had complete resolution of her symptoms over 1 year. Patient 2 presented with bilateral pulsatile tinnitus and vertigo and was found to have bilateral IAC exostoses. Patient 3 presented with hearing loss and tinnitus, and a unilateral IAC osteoma was ultimately discovered. Because of the mild nature of their symptoms, patients 2 and 3 were managed without surgery. We show that IAC osteomas can be differentiated from exostoses by radiographic evidence of bone marrow in high-resolution computed tomography scans, or by the presence of fibrovascular channels on histologic analysis. Management of these rare entities is customized on the basis of patient symptoms.
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Neoplasias Óseas/diagnóstico , Oído Interno/patología , Exostosis/diagnóstico , Osteoma/diagnóstico , Anciano , Neoplasias Óseas/cirugía , Craneotomía/métodos , Exostosis/cirugía , Femenino , Pérdida Auditiva Sensorineural/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Síndromes de Compresión Nerviosa/etiología , Osteoma/cirugía , Hueso Temporal/patología , Acúfeno/etiología , Tomografía Computarizada por Rayos X , Vértigo/etiología , Enfermedades del Nervio Vestibulococlear/etiologíaRESUMEN
Highly porous 3d transition metal oxide nanostructures are opening up the exciting area of oxygen evolution reaction (OER) catalysts in alkaline medium thanks to their good thermal and chemical stability, excellent physiochemical properties, high specific surface area and abundant nanopores. In this paper, highly porous Co-doped NiO nanorods were successfully synthesized by a simple hydrothermal method. The porous rod-like nanostructures were preserved with the added cobalt dopant ranging from 1 to 5 at% but were broken into aggregated nanoparticles at higher concentrations of additional cobalt. The catalytic activity of Co-doped NiO nanostructures for OER in an alkaline medium was assayed. The 5%Co-NiO sample showed a drastically enhanced activity. This result could originate from the combination of advantageous characteristics of highly porous NiO nanorods such as large surface area and high porosity as well as the important role of Co dopant that could provide more catalytic active sites, leading to an enhanced catalytic activity of the nanocatalyst.
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The present environmental crisis prompts the search for renewable energy sources such as solar-driven production of hydrogen from water. Herein, we report an efficient hybrid photocatalyst for water oxidation, consisting of a ruthenium polypyridyl complex covalently grafted on core/shell Fe@FeOx nanoparticles via a phosphonic acid group. The photoelectrochemical measurements were performed under 1 sun illumination in 1 M KOH. The photocurrent density of this hybrid photoanode reached 20 µA/cm2 (applied potential of +1.0 V vs reversible hydrogen electrode), corresponding to a turnover frequency of 0.02 s-1. This performance represents a 9-fold enhancement of that achieved with a mixture of Fe@FeOx nanoparticles and a linker-free ruthenium polypyridyl photosensitizer. This increase in performance could be attributed to a more efficient electron transfer between the ruthenium photosensitizer and the Fe@FeOx catalyst as a consequence of the covalent link between these two species through the phosphonate pendant group.