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Dermatopathic lymphadenopathy (DL) is well-known in inflammatory skin disease; however, it has not been reported in graft-versus-host disease (GvHD) after allogeneic stem cell transplantation. Here, we report 2 cases of DL in patients with acute GvHD of the skin and demonstrate complete donor chimerism of Langerhans cells within the lymph nodes.
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Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Células de Langerhans/patología , Linfadenopatía/diagnóstico , Linfadenopatía/etiología , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/etiología , Adulto , Biopsia , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Linfoma de Células T/complicaciones , Linfoma de Células T/diagnóstico , Linfoma de Células T/terapia , Masculino , Quimera por TrasplanteRESUMEN
AIM: Light microscopy is used as template in the evaluation and further development of medical imaging methods. Tissue shrinkage caused by histological processing is known to influence lung tissue dimensions. In diagnosis of COPD, computed tomography (CT) is widely used for automated airway measurement. The aim of this study was to compare histological and computed tomographic measurements of pig lung bronchi. METHODS: Airway measurements of pig lungs were performed after freezing under controlled inflation pressure in a liquid nitrogen bath. The wall thickness of seven bronchi was measured via Micro-CT and CT using the integral-based method (IBM) and the full-width-at-half-maximum method (FWHM) automatically and histologically on frozen and paraffin sections. Statistical analysis was performed using the Wilcoxon test, Pearson's correlation coefficient with a significance level at p<0.05, scatter plots and Bland-Altman plots. RESULTS: Bronchial wall thickness was smallest in frozen sections (median 0.71â mm) followed by paraffin sections (median 0.75â mm), Micro-CT (median 0.84â mm), and CT measurements using IBM (median 0.68â mm) and FWHM (median 1.69â mm). Statistically significant differences were found among all tested groups (p<0.05) except for CT IBM and paraffin and frozen sections and Micro-CT. There was high correlation between all parameters with statistical significance (p<0.05). CONCLUSIONS: Significant differences in airway measurement were found among the different methods. The absolute measurements with CT IBM were closest to the histological results followed by Micro-CT, whereas CT FWHM demonstrated a distinct divergence from the other groups.
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The neovascularization of tissues is accomplished by two distinct processes: de novo formation of blood vessels through the assembly of progenitor cells during early prenatal development (vasculogenesis), and expansion of a pre-existing vascular network by endothelial cell sprouting (angiogenesis), the main mechanism of blood vessel growth in postnatal life. Evidence exists that adult bone marrow (BM)-derived progenitor cells can contribute to the formation of new vessels by their incorporation into sites of active angiogenesis. Aim of this study was to investigate the in vitro self-organizing capacity of human BM mononuclear cells (BMMNC) to induce vascular morphogenesis in a three-dimensional (3D) matrix environment in the absence of pre-existing vessels. Whole BMMNC as well as the adherent and non-adherent fractions of BMMNC were embedded in fibrin gels and cultured for 3-4 weeks without additional growth factors. The expression of hematopoietic-, endothelial-, smooth muscle lineage, and stem cell markers was analyzed by immunohistochemistry and confocal laser-scanning microscopy. The culture of unselected BMMNC in 3D fibrin matrices led to the formation of cell clusters expressing the endothelial progenitor cell (EPC) markers CD133, CD34, vascular endothelial growth factor receptor (VEGFR)-2, and c-kit, with stellar shaped spreading of peripheral elongated cells forming tube-like structures with increasing complexity over time. Cluster formation was dependent on the presence of both adherent and non-adherent BMMNC without the requirement of external growth factors. Developed vascular structures expressed the endothelial markers CD34, VEGFR-2, CD31, von Willebrand Factor (vWF), and podocalyxin, showed basement-membrane-lined lumina containing CD45+ cells and were surrounded by alpha-smooth muscle actin (SMA) expressing mural cells. Our data demonstrate that adult human BM progenitor cells can induce a dynamic self organization process to create vascular structures within avascular 3D fibrin matrices suggesting a possible alternative mechanism of adult vascular development without involvement of pre-existing vascular structures.
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Células de la Médula Ósea/citología , Endotelio Vascular/embriología , Fibrina/metabolismo , Células Madre/citología , Adulto , Células de la Médula Ósea/metabolismo , Linaje de la Célula , Endotelio Vascular/citología , Humanos , Inmunohistoquímica , Microscopía Confocal , Morfogénesis , Células Madre/metabolismoRESUMEN
AIM: Tissue shrinking due to fixation and processing is well known. However, the degree of shrinking varies significantly with the tissue type as well as the processing method and is not well studied in various tissues. In daily pathological routine workflow, histological specimens from frozen and paraffin sections are performed from the same tissue. In the present study we compared the thickness of bronchus walls obtained from paraffin and frozen sections. METHODS: Pig lungs were frozen in ventilated condition in liquid nitrogen and 36 bronchi were isolated after dissection. Frozen sections of 5 µm thickness were performed and the remaining tissue was fixed and embedded in paraffin after fixation in 4% formalin. Frozen and paraffin sections from the same cutting edge were analysed after haematoxylin and eosin staining by measuring the wall thickness of the bronchi using high power fields of 400-fold magnification. In each bronchus 40 measurements were implemented at different wall positions distributed over the entire wall area. Summed up, in each group 1440 wall measurements were performed in total. Statistical analysis was conducted using the Wilcoxon test and t-test as well as Pearson's correlation coefficient with a significance level at P < 0.05. RESULTS: The bronchial wall thickness was significantly (p < 0.001) smaller in frozen sections (median: 0.50 mm; min: 0.37 mm; max: 0.97 mm) compared to paraffin sections (median: 0.58 mm; min: 0.35 mm; max: 1.06 mm). The median difference between paraffin and frozen sections was 0.05 mm (min: -0.11 mm; max: 0.22 mm). The wall thickness ratio of both groups was as follows: frozen/paraffin section = 0.8609, thus yielding a difference between paraffin and frozen of 13.91%. High correlation was found between wall thickness measurements on paraffin and frozen sections (R = 0.87, p < 0.001). CONCLUSIONS: The bronchus wall thickness in the frozen section was 14% reduced compared to the paraffin section. In routine pathology as well as in scientific studies these results are of relevance, as airway wall thickness represents a relevant marker for pathological interpretation, especially using CT image techniques.
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Bronquios/patología , Secciones por Congelación , Pulmón/patología , Adhesión en Parafina , Manejo de Especímenes/métodos , Animales , PorcinosRESUMEN
Incorporation of circulating hematopoietic progenitor cells (HPCs) into damaged skeletal muscle has been proposed as a novel mechanism of tissue repair complementary to satellite cell-dependent regeneration. We studied the occurrence and myoendothelial differentiation of HPCs in muscle of patients with inflammatory myopathies. Muscle biopsies from untreated patients with dermatomyositis, polymyositis, inclusion body myositis, and controls were investigated for the expression of endothelial (CD31, von Willebrand factor, vascular endothelial growth factor receptor 2), hematopoietic (CD34, CD133, CD45), and myogenic (Pax7, MyoD) markers by immunohistochemistry and reverse-transcriptase-polymerase chain reaction. Confocal laser scanning microscopy was used to visualize coexpression of CD34, CD133, von Willebrand factor, or Pax7 on individual cells. Morphometric analysis revealed significantly increased numbers of CD133 cells per square millimeter in polymyositis and inclusion body myositis compared with controls (p < 0.001); this correlated with the density of CD45 infiltrates (p < 0.001). By confocal laser scanning microscopy, we detected several mononuclear cells that coexpressed either CD34/von Willebrand factor or CD133/Pax7 with or without CD34 reactivity, indicating endothelial or myogenic commitment of some HPCs in skeletal muscle. Rarely, CD133/CD34/Pax7 cells seemed to occupy satellite cell niches or to incorporate into preexisting myofibers. Our findings suggest that circulating HPCs colonize skeletal muscle in inflammatory conditions and provide evidence for in situ myoendothelial differentiation of some of these cells.
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Diferenciación Celular/fisiología , Endotelio/fisiología , Células Madre Hematopoyéticas/patología , Células Madre Hematopoyéticas/fisiología , Músculo Esquelético/patología , Miositis/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos/genética , Antígenos/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Diferenciación Celular/efectos de los fármacos , Endotelio/efectos de los fármacos , Femenino , Expresión Génica/fisiología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Masculino , Microscopía Confocal , Persona de Mediana Edad , Músculo Esquelético/efectos de los fármacos , Miositis/clasificación , Factor de Transcripción PAX7/genética , Factor de Transcripción PAX7/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Factor de von Willebrand/inmunologíaRESUMEN
Here we discuss a case of arrhythmia-induced cardiomyopathy (AIC) with consecutive severe multiple organ failure. In relation to this imposing case, we discuss the significance of this potentially underestimated cause of newly occurred left-ventricular systolic dysfunction and concomitant arrhythmia. We further delineate the diagnostic algorithm and differential diagnoses of AIC.
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Arritmias Cardíacas/complicaciones , Cardiomiopatías/diagnóstico , Ventrículos Cardíacos/fisiopatología , Función Ventricular Izquierda/fisiología , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/cirugía , Cardiomiopatías/etiología , Cardiomiopatías/fisiopatología , Ablación por Catéter , Ecocardiografía Transesofágica , Electrocardiografía , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , SístoleRESUMEN
Separating wounded serosa by physical barriers is the only clinically approved adjunct for postoperative adhesion prevention. Since the optimal adhesion barrier has not been found, it is essential to improve our pathogenic understanding of adhesion formation and to compare the effects of different barrier materials on tissue and cells. Wistar rats underwent standardized peritoneal damage and were treated either with Seprafilm, Adept, Intercoat, Spraygel, SupraSeal or remained untreated as a control. 14 days postoperatively, the lesions were explanted and histomorphologically analyzed using the European ISO score to evaluate material implants. Striking differences between the material groups were present regarding the inflammation, fibrosis, and foreign body reaction. According to the ISO score, Intercoat and Spraygel were considered as nonirritating to tissue. Adept, Seprafilm, and SupraSeal were assessed as mild-irritating materials. Interestingly, the most effective material in adhesion prevention revealed moderate inflammation accompanied by minor fibrosis. The degree of inflammation to barrier materials does not predict the efficacy in the prevention of adhesions. Histopathological investigations are crucial to improve our understanding of the cellular mechanisms during adhesion formation and elucidate the tissue response to material approaches used in adhesion prevention. This will lead to improved antiadhesive strategies and the development of functional barrier biomaterials. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 598-609, 2018.
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Materiales Biocompatibles/farmacología , Ácido Hialurónico/farmacología , Peritoneo/efectos de los fármacos , Complicaciones Posoperatorias/tratamiento farmacológico , Adherencias Tisulares/tratamiento farmacológico , Animales , Femenino , Fibrosis/etiología , Fibrosis/patología , Reacción a Cuerpo Extraño/etiología , Reacción a Cuerpo Extraño/patología , Inflamación/etiología , Inflamación/patología , Membranas Artificiales , Peritoneo/cirugía , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/prevención & control , Ratas , Ratas Wistar , Adherencias Tisulares/patología , Adherencias Tisulares/prevención & controlRESUMEN
A 2 h single-tube, reverse-transcription(RT)-PCR/hybridization assay using the TaqMan format for rapid diagnostic screening of enterovirus (EV) infections was optimized for the real-time LightCycler (LC) technology. For low EV load clinical samples an additional 30 min reamplification step using a novel primer-mix/probe design resulted in a 100% concordance with AMPLICOR EV PCR Test and in-house RT-PCR. Combined with maximum specificity, the sensitivity of LC-PCR was 10- to 100-fold higher compared to AMPLICOR EV Test.
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Infecciones por Enterovirus/diagnóstico , Enterovirus/aislamiento & purificación , Colorantes Fluorescentes , Reacción en Cadena de la Polimerasa/métodos , Polimerasa Taq/metabolismo , Enterovirus/genética , Infecciones por Enterovirus/virología , Heces/virología , Humanos , Faringe/virología , ARN Viral/análisis , ARN Viral/sangre , ARN Viral/líquido cefalorraquídeo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
OBJECTIVES: Airway morphology shows characteristic changes in different pathologies. This study assesses the accuracy of a current automatic airway assessment technique by correlating CT images of porcine airways to histological slices of the same localization. MATERIALS AND METHODS: Four isolated and ventilated porcine lungs were frozen in a liquid nitrogen bath and examined with a CT scanner (MDCT). This technique both preserved normal radiomorphological appearance and made it possible to slice the specimens for histological examination for subsequent correlation. The parameters wall thickness (WT), wall percentage (WP), and total diameter (TD) were assessed by computer-aided measurement of the MDCT images using an integral-based method (IBM) and by manually measuring the histological slices with an electronic caliper. RESULTS: The radiological-pathological correlation could be performed for 16 localizations. Mean relative errors for WT, WP, and TD were 11%, 5.6%, and 8.5%, respectively. Correlation was very high with coefficients r of 0.951 for WT, 0.916 for WP, and 0.987 for TD. CONCLUSIONS: Our results are comparable to previously described errors in phantom correlations but are the first proof of ex vivo feasibility. Thus, by applying this freezing technique to MDCT data of diseased, explanted lungs and by combination with the IBM, further experiments can be performed to explore the effects of airway pathology on radiological morphology.
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Bronquios/patología , Broncoscopía/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Tráquea/diagnóstico por imagen , Tráquea/patología , Algoritmos , Animales , Técnicas In Vitro , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como Asunto , PorcinosRESUMEN
BACKGROUND: This study was conducted to investigate the dynamic process of new vessel formation, fundamental for tumor growth and metastasis, in head and neck squamous cell carcinoma (HNSCC). METHODS: We used immunohistochemistry, confocal laser-scanning microscopy, and reverse transcriptase-polymerase chain reaction to study endothelial cell and concomitant pericyte development with markers CD133, CD34, VEGFR-2, CD31, vWF, and STRO-1 in tumor and peritumoral tissues of 18 patients with HNSCC. RESULTS: Highly compressed and structurally abnormal vessels with barely any activity of new vessel formation were found in tumor tissue, whereas the adjacent peritumoral tissue vessels showed a normal architecture with tight endothelial cell-pericyte interaction and a high activity of angiogenesis. Endothelial precursor cells expressing CD133/VEGFR-2 could be incorporated into these newly formed vessels, forming cell clusters from which a thin endothelial lining could emanate. CONCLUSIONS: These data show a high activity of new vessel formation in the peritumoral stroma of HNSCC, with endothelial precursor cells being incorporated into these structures.
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Carcinoma de Células Escamosas/irrigación sanguínea , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Neovascularización Patológica , Antígeno AC133 , Adulto , Anciano , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Antígenos de Superficie/metabolismo , Carcinoma de Células Escamosas/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Glicoproteínas/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Persona de Mediana Edad , Péptidos/metabolismo , Pericitos/metabolismo , Pericitos/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , ARN/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Ischemic-type biliary lesions (ITBL) belong to a group of biliary disorders that are regarded as the major complication in patients with orthotopic liver transplantation (OLT). We performed histological evaluation of donor common bile ducts received during OLT to find morphological clues to the pathomechanisms of ITBL. We investigated 93 grafts of 92 patients (recipients: mean age, 56.5 years; underlying disease: hepatocellular carcinoma (n = 45), alcoholic cirrhosis (n = 16), viral hepatitis with cirrhosis (n = 9), retransplantations (n = 9), others (n = 14); donors: mean age, 53.2 years). Donor common bile ducts were received after recirculation of the hepatic artery prior to biliary end-to-end anastomosis and routinely processed. Statistical evaluation was performed by chi-square analysis and multivariate analysis using a logistic regression model. With regard to ITBL (observed in 19.4 %), the following phenomena were found to be statistically relevant: necrosis of the bile duct wall, arteriolonecrosis, vascular lesions (such as subintimal edema), and intramural bleeding (P < 0.001, P < 0.001, P = 0.029, and P = 0.031, respectively). In logistic regression analysis, arteriolonecrosis was the only parameter with significance (P = 0.001). Based on these results on the morphology of the donor common bile duct, we conclude that these phenomena of vascular damage, reflecting microangiopathy, play a major role in the pathogenesis of ITBL.
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Conductos Biliares/irrigación sanguínea , Conductos Biliares/patología , Trasplante de Hígado , Complicaciones Posoperatorias/patología , Adulto , Anciano , Femenino , Humanos , Isquemia/patología , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Donantes de TejidosRESUMEN
INTRODUCTION: The formation of peritoneal adhesions still is a relevant clinical problem after abdominal surgery. Until today, the most important clinical strategies for adhesion prevention are accurate surgical technique and the physical separation of traumatized serosal areas. Despite a variety of barriers which are available in clinical use, the optimal material has not yet been found. DISCUSSION: Mesothelial cells play a crucial physiological role in friction less gliding of the serosa and the maintenance of anantiadhesive surface. The formation of postoperative adhesions results from a cascade of events and is regulated by various cellular and humoral factors. Therefore, optimization or functionalization of barrier materials by developments interacting with this cascade on a structural or pharmacological level could give an innovative input for future strategies in peritoneal adhesion prevention. For this purpose, the proper understanding of the formal pathogenesis of adhesion formation is essential. Based on the physiology of the serosa and the pathophysiology of adhesion formation, the available barriers in current clinical practice as well as new innovations are discussed in the present review.
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Procedimientos Quirúrgicos del Sistema Digestivo/normas , Procedimientos Quirúrgicos Mínimamente Invasivos/normas , Enfermedades Peritoneales/prevención & control , Peritoneo/patología , Guías de Práctica Clínica como Asunto , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Humanos , Enfermedades Peritoneales/etiología , Enfermedades Peritoneales/patología , Adherencias TisularesRESUMEN
INTRODUCTION: Motility-related protein (MRP)-1/CD9 is implicated in cell adhesion and motility and was shown to be clearly involved in tumor prognosis and angiogenesis. Elevated MRP-1/CD9 expression on tumor cells has been linked to a favorable prognosis in breast cancer, colon cancer, lung cancer, and HNSCC. Because MRP-1/CD9 is associated with angiogenesis, it might play a role in tumor angiogenesis as well. METHODS: We analyzed MRP-1/CD9 expression in HNSCC specimens and cell lines by real-time RT-PCR and in HNSCC biopsy specimens and stromal vessels by immunohistochemistry. Kruskal Wallis and Chi2 test, univariate and multivariate Cox regression, and Kaplan-Meier methods were used for statistical analysis. RESULTS: Real-time and PCR RT showed elevated expression of MRP-1/CD9 in one (SCC25) of four HNSCC cell lines and two of six HNSCC patients, whereas two cell lines (SCC9 and JPPA) and one HNSCC patient had lower MRP-1/CD9 levels compared with other specimens. Immunohistochemistry demonstrated strong MRP-1/CD9 IR expression on tumor cells in 13 patients (39%), whereas 21 patients (61%) had less to medium MRP-1/CD9 IR expression. Increased MRP-1/CD9 expression on tumor cells was correlated with prolonged patient survival (p =.02) and a longer disease-free interval (p =.004), a diminished recurrence rate (p =.02), and lower stages of neck lymph nodes (p =.04). MRP-1/CD9 IR was also found in a subpopulation of vessels that seem to be less in tumor specimens than in normal mucosa (p <.0001). MRP-1/CD9+ vessels are podoplanin+ and are therefore regarded as lymphatic vessels. CONCLUSIONS: Our results revealed that elevated MRP-1/CD9 expression on HNSCC is linked to a favorable clinical outcome and confirmed reports of MRP-1/CD9 expression in other carcinomas. MRP-1/CD9+ vessels were found to be lymphatic in nature. The number and staining intensity of these vessels is decreased in tumor tissue, which suggests a stabilizing role for this protein in lymphangiogenesis.
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Antígenos CD/análisis , Carcinoma de Células Escamosas/química , Neoplasias de Cabeza y Cuello/química , Glicoproteínas de Membrana/análisis , Adulto , Anciano , Antígenos CD/genética , Movimiento Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tetraspanina 29 , Células Tumorales CultivadasRESUMEN
BACKGROUND AND METHODS: VEGF proteins and their receptors are involved in tumor vessel neoformation. The third VEGF receptor, VEGFR3 (flt-4) is important during both blood vessel development and lymphatic vessel formation. Because HNSCC preferentially metastasizes to regional lymph nodes, we investigated the expression of VEGFR3 and its ligand VEGF-C in head and neck squamous cell carcinomas by semiquantitative RT-PCR (4 HNSCC cells lines and 6 HNSCC specimens) and by immunohistochemistry (18 HNSCC specimens). VEGFR3 protein expression was confirmed by Western blotting in four HNSCC cell lines and six HNSCC specimens. RESULTS: Semiquantitative mRNA analysis showed VEGF-C mRNA expression in three (SCC9, SCC25, LFFR) of four HNSCC cell lines and all six HNSCC specimens. VEGFR3 mRNA was found in two HNSCC cell lines (JPPA and SCC25) and only weakly detected in the other two HNSCC cell lines (SCC9 and LFFR). High amounts of VEGFR3 mRNA were shown in all six patients' tumor specimens. VEGFR3 Western blot analysis yielded a distinct band at the predicted size of 210 kD in JPPA and SCC9 and hardly detectable bands in SCC25 and LFFR cell lines. All six HNSCC specimens displayed strong VEGFR3 protein bands. Immunohistochemistry in 18 HNSCC specimens assigned strong to mediate VEGF-C IR and minor VEGFR3 IR to tumor cells and strong VEGF-C and VEGFR3 IR to tumor surrounding vessels. In addition, intense VEGF-C immunostaining was observed on perivascular and mononuclear cells in the tumor surrounding stroma. Subtyping of VEGFR3+ microvascular tumor vessels revealed partially double immunolabeling with CD34 and flk-1, indicating a common origin of blood and lymphatic vessels. The expression of VEGF-C on tumor cells could be correlated with recurrences, and larger primary tumors had more VEGF-C-positive vessels. CONCLUSIONS: The broad expression of VEGF C and VEGFR3 in HNSCC suggests involvement in tumor lymph angiogenesis and vascular angiogenesis, promoting tumor growth and propagation of cancer cells. This implies that inhibitors of lymph angiogenesis could become effective therapeutic options similar to classical angiogenesis inhibitors.
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Carcinoma de Células Escamosas/metabolismo , Factores de Crecimiento Endotelial/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD34/metabolismo , Western Blotting , Humanos , Inmunohistoquímica , Persona de Mediana Edad , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Factor C de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: To find evidence for the presence of endothelial precursor cells, which can induce new vessel formation, in the synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Precursor cells in the synovial tissue of 18 RA patients and 15 OA patients were identified by immunohistochemistry, morphometric analysis, and confocal laser scanning microscopy using the following phenotype markers: CD31, CD34, STRO-1, CD133, vascular endothelial growth factor receptor 2 (VEGFR-2), and CXCR4. The presence of CD31, CD34, CD133, VEGFR-2, and CXCR4 messenger RNA in the synovial tissue was determined by reverse transcriptase-polymerase chain reaction, and the message for CXCR4 was quantified by an RNase protection assay. RESULTS: A population of cells that expressed CD34 on their surface but lacked the endothelial cell marker CD31 was found in the synovial tissue of RA and OA patients. CD34+,CD31- cells were detected in close proximity to STRO-1+ and CD133+ cells, forming cell clusters in the sublining area of the synovial membrane. Within these cell clusters, CD34+,CD31- precursor cells were located on the inside surrounded by STRO-1+ cells and with CD133+ cells on the outside. CD34+ precursor cells in the cell layer expressed high levels of the chemokine receptor CXCR4, while VEGFR-2 was expressed on CD34+ and CD133+ cells, and alpha-smooth muscle actin was expressed on STRO-1+ cells. CONCLUSION: The presence of endothelial precursor cells in the synovial tissue of RA and OA patients provides evidence for vasculogenesis induced by precursor cells that arise in situ or from circulating progenitors.