Immunomodulatory effect of IL-2 induced bone marrow mononuclear cell therapy on control of allergic asthma

Asthma is a chronic airway disease. Allergic reactions and T helper (h)2 immune response play a key role in asthma occurrence. Cell therapy can control inflammation and remodeling responses in allergic asthma, and cytokines can change this effect. Therefore, in this study, the effect of treated cell therapy with IL-2 to control allergic asthma was studied. Bone marrow cells were extracted and co-cultured with IL-2 and the cells were used via intra-tracheal administration in allergic asthma mice. Levels of IL-4, IL-5, IL-13, Leukotriene B4 and C4, and remodeling factors were measured. At least, a histopathology test of lung tissue was done. Type2 cytokines, leukotrienes, remodeling factors, mucus secretion, goblet cell hyperplasia, peri-bronchial and peri-vascular inflammation were significantly (p˂0.05) decreased by treating with bone marrow-derived mononuclear cells (BMDMCs) and IL-2-BMDMCs. Treatment with IL-2-BMDMCs could significantly decrease IL-13, transforming growth factor (TGF)-β, HP levels, and mucus secretion (p˂0.05) compared to BMDMCs treatment. In this study, BMDMCs and IL-2-BMDMCs therapy could decrease inflammation, allergic, and remodeling factors in allergic asthma. Cell therapy with BMDMCs had a strong and notable effect on the control of allergic asthma pathophysiology when co-cultured and used with IL-2 (AU)

Dermatosis neutrofílica y síndrome mielodisplásico / Neutrophilic dermatosis and myelodysplastic syndrome

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Papel de las células madre en el tratamiento de la incontinencia urinaria / The role of stem cells in the treatment of urinary incontinence

Objetivo: valorar el estado actual del tratamiento de la incontinencia urinaria en estudios de experimentación animal y clínica. Revisión: en el mundo hay más de 200 millones de mujeres con incontinencia urinaria, circunstancia que limita la calidad de vida. La incontinencia urinaria de esfuerzo es el tipo de incontinencia más frecuente. En los últimos años se ha propuesto el tratamiento con células madre habiendo sido objeto de trabajos de experimentación animal y clínicos. Se realiza una revisión crítica de las ventajas e inconvenientes de la utilización de células autólogas procedentes de medula ósea, tejido graso, muscular y de cordón umbilical. Se valoran las vías de administración y la metodología utilizada, proponiendo nuevas formas de administración y de los trabajos clínicos, mecanismos de acción y potenciales efectos secundarios. Por último se analizan los dispares resultados clínicos que oscilan entre el 88,9% y el 13,2%. Conclusión: el tratamiento de la incontinencia urinaria con células madre en el futuro podría colaborar a mejorar la calidad de vida de estas pacientes (AU)

Objective: Study the actual status of the urinary incontinence treatment with stem cells on animal and clinical experience. Review: More than 200 million people worldwide, affected with urinary incontinence with reduced quality of life. Stress urinary incontinence has been reported as the most common type of urinary incontinence. Stem cell for the regenerative repair of the stress urinary incontinence has been proposed during the last years, many experimental studies on animal models and some in clinical. This is a critical review of advantages and disadvantages of autologous cells use from bone marrow, fat tissue, muscle and umbilical cord. Administration ways and procedures are described and methology of administration with new ways of treatments are proposed. Study designs are discussed in terms of action mechanisms and possible disadvantages. Finally, discordant results ranging from 88.9% to 13.2% improvement rates are discussed. Conclusion: Urinary stress incontinence treatment with stem cells in the future could improve the quality of life of this kind of patients (AU)

Bone marrow-derived cells are recruited by the melanoma tumor with endothelial cells contributing to tumor vasculature

Purpose. Tumor expansion is dependent on neovascularization, a process that requires sustained new vessel formation. Although the critical role of angiogenesis by endothelial sprouting in this process, controversy still prevails on whether angiogenesis involving bone marrow-derived endothelial cells, does contribute to this process. This study aims to evaluate the recruitment of bone marrow-derived cells by the melanoma tumor, including endothelial cells, and if they contribute to angiogenesis. Methods. A chimeric mouse model of GFP bone marrow was used to induce melanoma tumors derived from murine B16-F10 cell line. These tumors were evaluated for the presence of myeloid cells (CD11b), T lymphocytes (CD3, CD4 and CD8) and endothelial cells (VEGFR2 and CD31) derived from bone marrow. Results. Mice transplanted with GFP+ cells showed significant bone marrow chimerism (90.9 ± 0.87 %) when compared to the GFP transgenic mice (90.66 ± 2.1 %, p = 0.83) demonstrating successful engraftment of donor bone marrow stem/progenitor cells. Analysis of the murine melanoma tumor showed the presence of donor cells in the tumors (3.5 ± 1.7 %) and interestingly, these cells represent endothelial cells (CD31+ cells; 11.5 ± 6.85 %) and myeloid cells (CD11b+ cells; 80 ± 21 %), but also tumor-infiltrating lymphocytes (CD8+ T cells, 13.31 ± 0.2 %; CD4+ T-cells, 2.1 ± 1.2 %). Examination of the tumor endothelium by confocal microscopy suggests the presence of donor CD31+/GFP+ cells in the wall of some blood vessels. Conclusion. This study demonstrates that bone marrow-derived cells are recruited by the murine melanoma tumor, with myeloid cells and CD4 and CD8 T lymphocytes migrating as antitumor immune response, and endothelial cells participating of the tumor blood vessels formation (AU)

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Alteraciones en el número de copias en pacientes adultos con leucemia linfoblástica aguda B madura, tratados con inmunoquimioterapia específica / Copy number alterations in adult patients with mature B acute lymphoblastic leukemia treated with specific immunochemotherapy

Fundamento y objetivo: A diferencia del linfoma de Burkitt, las alteraciones moleculares distintas a los reordenamientos de C-MYC apenas se han estudiado en pacientes con leucemia linfoblástica aguda B (LLA-B) madura. El objetivo de este estudio fue analizar la frecuencia y el significado pronóstico de las copy number alterations (CNA, «alteraciones del número de copias») en genes clave de la diferenciación de los linfocitos, ciclo celular y supresores de tumores en pacientes adultos. Pacientes y métodos: Se analizaron, por amplificación de sondas dependiente de ligamento múltiple, muestras de médula ósea en el momento del diagnóstico de 25 adultos con LLA-B madura tratados con rituximab y quimioterapia específica. Resultados: Las CNA más frecuentes fueron las alteraciones en la región 14q32.33 (11 casos, 44%), seguidas de las alteraciones en los genes reguladores del ciclo celular CDKN2A/B y RB1 (16%). No se encontró correlación entre la presencia de estas CNA y las características clínico-biológicas o de respuesta al tratamiento. Conclusiones: La alta frecuencia de alteraciones en la región 14q32.33, CDKN2A/B y RB1 encontradas en este estudio podría explicar la agresividad e invasividad de la LLA-B madura (AU)

Background and objective: Unlike Burkitt lymphoma, molecular abnormalities other than C-MYC rearrangements have scarcely been studied in patients with mature B acute lymphoblastic leukemia (B-ALL). The aim of this study was to analyze the frequency and prognostic significance of copy number alterations (CNA) in genes involved in lymphoid differentiation, cell cycle and tumor suppression in adult patients with B-ALL. Patients and methods: We have analyzed by multiplex ligation-dependent probe amplification the genetic material from bone marrow at diagnosis from 25 adult B-ALL patients treated with rituximab and specific chemotherapy. Results: The most frequent CNA were alterations in the 14q32.33 region (11 cases, 44%) followed by alterations in the cell cycle regulator genes CDKN2A/B and RB1 (16%). No correlation between the presence of specific CNA and the clinical-biologic features or the response to therapy was found. Conclusions: The high frequency of CNA in the 14q32.33 region, CDKN2A/B and RB1 found in our study could contribute to the aggressiveness and invasiveness of mature B-ALL (AU)

Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia

Purpose: Pentoxifylline (PTX) has been shown to increase chemotherapy-induced apoptosis. A clinical trial was developed to evaluate the effect of the addition of PTX to the induction steroid window phase in children with acute lymphoblastic leukemia (ALL). Methods: Thirty-two children were enrolled on this study. Children with a new diagnosis of ALL were randomly assigned to receive prednisone (PRD) 40 mg/m2/day only during the 7-day treatment pre-phase (PRD group, 11 patients) or to receive PRD with PTX (10 mg/kg/day) (PTX group, 11 patients); the control group included children with normal bone marrow (10 patients). Bone marrow aspiration (BMA) was performed at diagnosis (day -7) in all groups, and at day 0 (end of PRD window) for patients with ALL (PRD and PTX groups). Apoptosis was evaluated by flow cytometry (FC) using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) stains. Statistical analysis was performed using the Mann–Whitney U test. Results: Apoptotic index at day -7 was similar in all groups. However, at day 0 post-treatment, apoptosis was significantly higher in the PTX group than in the PRD group (p < 0.001). There were no serious adverse effects associated with PTX. Conclusions: PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase (AU)

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Potencial terapéutico de las células madre derivadas de la médula ósea en el infarto cerebral / Therapeutic potential of bone marrow stem cells in cerebral infarction

Introducción. Las células madre constituyen una alternativa terapéutica que se encuentra en fase de experimentación para el infarto cerebral. Objetivo. Mostrar la evidencia científica existente sobre el potencial terapéutico de las células madre de la médula ósea en esta enfermedad. Desarrollo. El infarto cerebral representa el 80% de las enfermedades cerebrovasculares. La trombólisis constituye la única terapia aprobada, pero, por su estrecha ventana terapéutica, sólo se aplica a un bajo porcentaje de los pacientes. De manera alternativa, los tratamientos neurorrestauradores, como el de células madre, pueden aplicarse en períodos más prolongados. Por esta razón se efectuó una búsqueda bibliográfica en PubMed con el empleo de las palabras clave ‘stem cells’, ‘bone marrow derived mononuclear cells’ y ‘stroke’. Se encontraron evidencias de seguridad y eficacia de dichas cé- lulas en diferentes momentos evolutivos del infarto cerebral. Se identificaron estudios que en clínica y preclínica las recolectaron por punción medular y en sangre periférica, y las trasplantaron directamente en el área infartada o por vía intravascular. El efecto terapéutico se relaciona con sus propiedades de plasticidad celular y liberación de factores tróficos. Conclusiones. El concentrado de células mononucleares autólogas, obtenido en sangre periférica o por punción de la médula ósea, y trasplantado por vía intravenosa, es una factible opción metodológica que permitirá rápidamente incrementar el número de ensayos clínicos en diferentes etapas evolutivas del infarto cerebral. Esta terapia muestra seguridad y eficacia; sin embargo, deben ampliarse las evidencias que avalen su generalización en humanos (AU)

Introduction. Stem cells are an alternative therapy for cerebral infarction that is still in the experimental phase. Aims. To report on the existing scientific evidence on the therapeutic potential of bone marrow stem cells in this disease. Development. Cerebral infarction accounts for 80% of cerebrovascular diseases. Thrombolysis is the only approved therapy, but, owing to its narrow therapeutic window, it is only applied to a low percentage of patients. Conversely, neurorestorative treatments, such as stem cells, can be applied over longer periods of time. For this reason a literature search was conducted on PubMed using the key words ‘stem cells’, ‘bone marrow derived mononuclear cells’ and ‘stroke’. Evidence was found of the safety and effectiveness of such cells at different points in the development of the completed stroke. Results included studies that, in the clinical and preclinical period, collected them by spinal puncture and in peripheral blood, and transplanted them either directly into the infarcted area or intravenously. The therapeutic effect is related with their cell plasticity and trophic-factor releasing properties. Conclusions. Autologous mononuclear cell concentrate, obtained from peripheral blood or by puncturing the bone marrow and transplanted intravenously, is a feasible methodological option that will make it possible to quickly increase the number of clinical trials conducted at different stages of the development of a completed stroke. This therapy has proved itself to be safe and effective; nevertheless, further evidence is needed to endorse its generalised use in humans (AU)

A tête-a tête between cancer stemm cells and endothelial progenitor cells in tumor angiogenesis

Accumulating evidence suggests the involvement of stem cells in tumor angiogenesis. Two major types of stem cells frequently discussed in this regard are bone marrow-derived endothelial progenitor cells (EPCs) and tumor-derived cancer stem cells (CSCs). The present review discusses the possibility of a close association between these two cell types that drives the tumor towards metastasis. An exploration of this plausible relationship between EPCs and CSCs is imperative to completely unveil the mechanisms of tumor angiogenesis and develop CSC- and/or EPC-targeted anti-tumor therapies (AU)

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Effects of human milk on blood and bone marrow cells in a malnourishedmice model; comparative study with cow milk / Efecto de la leche humana sobre células de sangre y de médula ósea en un modelo de ratos desnutridos; estudio comparativo con leche de vaca

Introduction: It has been demonstrated that the alterations caused by nutrient deficiency can be reverted by adequate nutritional repletion. Objective: To perform comparative studies between human and cow milks in order to evaluate the impact of both milks on the recovery of blood and bone marrow cells affected in malnourished mice. Method: Weaned mice were malnourished after consuming a protein free diet for 21 days. Malnourished mice received cow or human milk (CM or HM) for 7 or 14 consecutive days. During the period of administration of milk, the mice consumed the protein free diet ad libitum. The malnourished control (MNC) group received only protein free diet whereas the well-nourished control (WNC) mice consumed the balanced conventional diet. Results and Discussion: Both milks normalized serum albumin levels and improved thymus weight. Human milk was less effective than cow milk to increase body weight and serum transferrin levels. In contrast, human milk was more effective than cow milk to increase the number of leukocytes (WNC: 6.90 ± 1.60a; MNC: 2.80 ± 0.90b; CM 7d: 3.74 ± 1.10b; HM 7d: 7.16 ± 1.90a; CM 14d: 4.35 ± 1.20b; HM 14d: 6.75 ± 1.20a (109/L);p < 0.05) and lymphocytes (WNC: 5.80 ± 0.36a; MNC: 1.80 ± 0.40b; CM 7d: 2.50 ± 0.30b; HM 7d: 4.20 ± 0.50c; CM 14d: 3.30 ± 0.31d; HM 14d: 4.70 ± 0.28c (109/L);p < 0.05) in peripheral blood. Both milks induced an increment in mitotic pool cells in bone marrow and α-naphthyl butyrate esterase positive cells in peripheral blood. They also normalized phagocytic function in blood neutrophils and oxidative burst in peritoneal cells. Conclusion: Both milks were equally effective to exert favorable effects on the number of the bone marrow cells and the functions of the blood and peritoneal cells involved in immune response. However, only human milk normalized the number of leukocytes and increased the number of neutrophils in peripheral blood (AU)

Introducción: Las alteraciones causadas por la deficiencia de nutrientes pueden ser revertidas por un aporte nutricional adecuado. Objetivos: Realizar estudios comparativos entre leche humana y leche de vaca para evaluar su impacto en la recuperación de las células de sangre y de médula ósea afectadas en ratones desnutridos. Métodos: Los ratones fueron desnutridos al recibir una dieta libre de proteínas durante 21 días a partir del destete. Posteriormente, estos ratones desnutridos recibieron leche de vaca (LV) o leche humana (LH) durante 7 o 14 días consecutivos, mientras continuaban consumiendo la dieta libre de proteínas ad libitum. El grupo control de desnutrición (CD) sólo recibió la dieta libre de proteínas mientras que los ratones controles bien nutridos (CBN) consumieron la dieta balanceada convencional. Resultados y Discusión: Ambas leches normalizaron los niveles de albumina sérica e incrementaron el peso del timo. La leche humana fue menos efectiva que la leche de vaca para incrementar el peso corporal y los niveles de transferrina en suero. Sin embargo, la leche humana fue más efectiva para incrementar el número de leucocitos (CBN: 6,90 ± 1,60a; CD: 2,80 ± 0,90b; LV 7d: 3,74 ± 1,10b; LH 7d: 7,16 ± 1,90a; LV 14d: 4,35 ± 1,20b; LH 14d: 6,75 ± 1,20a (109/L);p < 0,05) y linfocitos (CBN: 5,80 ± 0,36a; CD: 1,80 ± 0,40b; LV 7d: 2,50 ± 0,30b; LH 7d: 4,20 ± 0,50c; LV 14d: 3,30 ± 0,31d; LH 14d: 4,70 ± 0,28c (109/L); p < 0,05) en sangre periférica. Ambas leches indujeron un incremento de las células del compartimiento mitótico de médula ósea y de las células ±-naftil butirato esterasa positivas en sangre periférica. Además, normalizaron la función fagocítica en neutrófilos de sangre periférica y el estallido oxidativo en las células peritoneales. Conclusiones: Ambas leches fueron igualmente efectivas para ejercer efectos favorables en el número de las células de la médula ósea y en las funciones de las células peritoneales y de la sangre involucradas en la respuesta inmune. Sin embargo, sólo la leche humana normalizó el número de leucocitos e incrementó el número de neutrófilos en sangre periférica (AU)

Mesenchymal niches of bone marrow in cancer

Over the last decade, genetic and cell biology studies have indicated that tumour growth is not only determined by malignant cancer cells themselves, but also by the tumour microenvironment. Cells present in the tumour microenvironment include fibroblasts, vascular, smooth muscle, adipocytes, immune cells and mesenchymal stem cells (MSC). The nature of the relationship between MSC and tumour cells appears dual and whether MSC are pro- or anti-tumorigenic is a subject of controversial reports. This review is focused on the role of MSC and bone marrow (BM) niches in cancer (AU)

Interleukin-15 enhances T-cell responses by stimulation with dendritic cells

INTRODUCTION: Cytokines play important roles in regulating immune responses. Interleukin-2 (IL-2) has usually been used as an adjuvant to enhance antitumour immune responses. However, its crucial role in activation-induced cell death, inhibition of homeostatic proliferation of CD8+ memory T cells and its notable biological side effects impair its prospect of application. IL-15 has several similar functions to IL-2 and shows potential advantages over IL-2, and is being investigated to enhance antitumour dendritic cell (DC) vaccine strategies in our ongoing studies. OBJECTIVE: In this preliminary study, we evaluated the ability of IL-15, compared with IL-2, to act as an adjuvant to enhance T-cell responses activated by DCs in vitro. MATERIALS AND METHODS: Bone marrow-derived DCs (BMDCs) were pulsed with tumour antigens and used to stimulate lymphocyte responses in the presence of IL-15 or IL-2. The activated T lymphocytes were examined by flow cytometric analysis, and interferon-γ (IFN-γ) enzyme-linked immunospot and cytotoxicity assays. RESULTS: IL-15 was observed to activate lymphocytes with comparable phenotype characteristics of activated/memory CD8+ lymphocytes, compared with IL-2. Both in primary and secondary stimulation with DCs, when using IL-15 as an adjuvant, activated lymphocytes showed higher proportions of IFN-γ-secreting subsets. In secondary stimulation with BMDCs in the presence of IL-15, the activated lymphocytes showed a stronger cytotoxicity to antigen-specific tumour target cells. CONCLUSIONS: Our study suggested that IL-15 might be a prospective adjuvant for a DC vaccine strategy against cancers. The further observation that IL-15 acts as an adjuvant for an antitumour DC vaccine strategy is worth investigating (AU)

Differentiation of mesenchymal stem cells to insulin-producing cells and their impact on type 1 diabetic rats

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Cell therapy is thought to be a possible approach for treatment of diabetes. Cells with the ability to differentiate into insulin-producing cells (IPCs) would provide an unlimited source of islet cells for transplantation. In this study, the differentiation capacity of rat bone-marrow-derived mesenchymal stem cells (MSCs) to IPCs and the feasibility of using them for reversal of hyperglycemia were investigated. In vitro studies indicated that treatment of cells with high glucose concentration, nicotinamide and Beta-mercaptoethanol resulted to differentiated cells, which had characteristics of IPCs including spherical, grape-like morphology, secretion of insulin, and being positive for dithizone. To test the in vivo function of differentiated MSCs, they were injected into the spleen of diabetic rats. It was shown that diabetic rats who received IPCs, significantly reduced the glucose level, in response to intraperitoneal glucose tolerance (IPGT) test. These results indicate that MSCs are capable of in vitro differentiation into functional IPCs, which can reverse hyperglycemia in rat model of diabetes (AU)

Liquen plano oral y dendrocitos dérmicos / Oral lichen Planus and Dermal Dendrocytes

Introducción: El liquen plano oral (LPO) es una enfermedad inflamatoria relativamente frecuente que se presenta con un amplio abanico de formas clínicas. Todavía no se ha determinado completamente su patogenia, aunque se sabe que los linfocitos actúan de mediadores con la participación de citoquinas y otras células inflamatorias, entre ellas los dendrocitos dérmicos (DD) tipo I y tipo II (DD positivos para el factor XIIIA y CD34, respectivamente).Objetivos. Describir la presencia y distribución de estas células en el tejido, mediante técnicas inmunohistoquímicas, en 23 muestras procedentes de pacientes que reunían los criterios clínicos e histopatológicos de LPO. Resultados: Los DD factor XIII+ estaban localizados principalmente en la dermis superficial (p < 0,0001) y no en la submucosa profunda. Dichas células se encontraban en abundancia en toda la unión dermoepidérmica y se relacionaban estrechamente con la infiltración linfocitaria. Los DD factor XIIIa+ se encontraban además en el epitelio y la dermis profunda. En cambio, los DD CD34+ se distribuyeron principalmente en la dermis profunda, directamente por debajo del infiltrado linfocitario, con pocas células en la zona subepitelial. Conclusiones: Los DD estaban presentes en el LPO, con diferentes distribuciones en los tejidos. Así, los DD factor XIIIa+ predominaban en la dermis superficial, mientras que los DD CD34+ se encontraban principalmente en la dermis profunda. Esto apunta a que los DD, y sobre todo los DD factor XIIIa+ debido a su capacidad para expresar moléculas de adhesión intercelulares-1 (ICAM-1) y el factor de necrosis tumoral alfa (TNF-α), pueden desempeñar una función destacada en la patogénesis del LPO (AU)

Introduction: Oral lichen planus (OLP) is a relatively common inflammatory disease with a wide range of clinical forms. Its pathogenesis has not been fully elucidated although it is known to be mediated by lymphocytes with the participation of cytokines and other inflammatory cells, including type I and type II dermal dendrocytes (DD) (factor xiIIa+ DD and CD34+ DD, respectively). Objectives: To describe the presence and tissue distribution of these cells, through immunohistochemistry, in 23 specimens from patients with clinical and histopathological criteria of OLP. Results: Factor xiIIa+ DD were mainly located in the superficial dermis (p < 0.0001) as opposed to the deep submucosa. These cells were abundant throughout the dermal-epidermal junction and closely related to lymphocyte infiltration. Moreover, factor xiIIa+ DD were also found in the epithelium and deep dermis. CD34+ DD were distributed mostly to the deep dermis directly below the lymphocyte infiltrate with few cells in the subepithelial region. Conclusions: DD were present in OLP, with distinct tissue distributions. Factor xiIIa+ DD were predominant in the superficial dermis while CD34+ DD could be found mostly in the deep dermis. These findings suggest that DD, and those positive for factor xiIIa+ in particular in view of their ability to express intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor α (TNF-α), may play an important role in pathogenesis of OLP (AU)

Impacto de la obstrucción microvascular persistente en el remodelado ventricular postinfarto tras el implante intracoronario de células mononucleadas de médula ósea: un estudio de cardiorresonancia con contraste / Effect of Persistent Microvascular Obstruction on Post-Infarction Ventricular Remodeling Following Intracoronary Bone-Marrow Cell Transplantation: a Contrast-Enhanced Cardiac Magnetic Resonance Study

Introducción y objetivos. La cardiorresonancia magnéticacon realce tardío de contraste (RMc) permite la detecciónprecoz de obstrucción microvascular persistente(OMP) tras un infarto. Hemos analizado el impacto de laOMP en el remodelado ventricular de una cohorte de pacientes con infarto agudo de miocardio con ST elevado(IAMSTE) que recibieron implante intracoronario de células mononucleadas de médula ósea autóloga (CMMOA).Métodos. Catorce pacientes recibieron infusión intracoronaria de 66 ± 39 millones de CMMOA a los 8 ± 2 días de un IAMSTE revascularizado con éxito (flujo TIMI 3 epicárdico). Se realizaron estudios seriados de RMc con gadolinio- DTPA (basal y a los 10 meses del infarto), con análisis de volúmenes y fracción de eyección ventricular izquierda, motilidad regional, tamaño del infarto y presenciade OMP (definida como un área con ausencia de señalen el seno del infarto).Resultados. Se detectó OMP en 5 (36%) de los 14 pacientes,junto con una tendencia en el estudio basal a presentar un mayor tamaño del infarto, mayores volúmenes y peor función sistólica general y regional de ventrículo izquierdo respecto a aquellos sin OMP. En el seguimiento, la presencia de OMP se relacionó significativamente con un incremento en el volumen telediastólico (25 ± 24 frente a –2 ± 19 ml; p = 0,037), ausencia de incremento en el grosor telediastólico parietal (p = 0,027) y una menor reducciónen el número de segmentos acinéticos o discinéticos.Conclusiones. La OMP evaluada precozmente medianteRMc tras un IAMSTE revascularizado con éxito seasocia con un remodelado ventricular izquierdo adversoen pacientes sometidos a implante intracoronario de CMMOA

Introduction and objectives. Late contrast-enhancedcardiac magnetic resonance (CMR) enables areas ofpersistent microvascular obstruction (PMO) to bedetected early after acute myocardial infarction. Our aimwas to evaluate the impact of PMO on subsequentventricular remodeling in a cohort of patients with acuteST-elevation myocardial infarction (STEMI) whounderwent intracoronary autologous bone-marrowmononuclear cell (ABMMC) transplantation.Methods. In total, 14 patients underwent intracoronarytransplantation of 66±39 × 106 ABMMCs 8±2 daysfollowing successful revascularization of a STEMI (i.e.,TIMI flow grade 3 in the affected artery). Serial CMRstudies with gadolinium-DTPA enhancement wereperformed at baseline and 10 months after infarction. Left ventricular volume and ejection fraction, regionalcontractility and the infarct size were measured and thepresence of PMO (defined as hypoenhanced areas withinthe infarcted zone) was investigated.Results. Overall, PMO was detected in five of the 14patients (36%). Those with PMO tended to have a largerinfarct size, larger ventricular volumes, and poorer regional and global left ventricular systolic function in baseline studies than those without PMO. At follow-up, there were significant associations between PMO and an increase in end-diastolic volume (25±24 mL vs. –2±19 mL; P=.037), the absence of an increase in end-diastolic parietal thickness (P=.027), and a smaller reduction in the number of akinetic or dyskinetic segments.Conclusions. The detection of PMO by CMR earlyafter successful revascularization of a STEMI in patientswho underwent intracoronary ABMMC transplantationwas associated with adverse left ventricular remodeling

Ectima gangrenoso e hiperdiploidía en médula ósea / Ecthyma gangrenosum and hyperploidy in bone marrow

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Leishmaniasis visceral en un hospital infantil entre 1994 y 2004 / Visceral leishmaniasis in a children´s hospital between 1994 and 2004

Objetivo. Conocer la incidencia de leishmaniasis visceral infantil en nuestro Hospital en los últimos 10 años y compararlo con estudios previos publicados. Material y métodos. Se realiza un estudio descriptivo retrospectivo de los casos de leishmaniasis infantil entre 1993 y junio 2004 en nuestro Hospital. Se obtienen 18 casos de los que recogemos los siguientes datos: edad, sexo, domicilio, antecedentes personales, clínica, exploración, pruebas complementarias, diagnóstico, tratamiento y seguimiento. Resultados. La incidencia de la enfermedad fue de 2-3 casos al año, con un pico máximo en el 2002; la mayoría procedían de Madrid, encontrándose sólo en dos casos antecedentes de interés. En la serie obtenida 11 fueron varones y 7 mujeres, con un rango de edad entre los 4 meses y los 9 años. La fiebre se presentó en todos los pacientes acompañándose de otros síntomas como astenia y anorexia; en la exploración física destacó la esplenomegalia, seguida de la palidez cutánea y hepatomegalia. En los parámetros sanguíneos todos presentaron anemia y en algunos casos otros datos como plaquetopenia, leucopenia, transaminasas e IgG elevadas. En todos los casos fue positivo el aspirado de médula ósea; de éstos un 78% tenía antícuerpos antileishmania positivos. El tratamiento de elección en 17 casos fue antimoniato de meglumina y un caso anfotericina B. Conclusiones. La leishmaniasis continúa siendo un problema en nuestro medio, afectando a niños con edades comprendidas entre 1 y 3 años por la vulnerabilidad de sus sistema inmune y sin tener una historia de contagio aparente (AU)

Objective. Knowing the incidence of the visceral leishmaniasis in children within our hospital in the last 10 years and comparing it with previous papers. Children and methods. A retrospective study of cases with leishmaniasis between 1993 and June of 2004 in our hospital has been carried out. 18 cases have been obtained, the following features have been collected for them: age, sex, address, personal records, symptoms, physical examination, laboratory testing, diagnosis, treatment and monitoring. Results. The disease incidence was 2-3 cases annually, with the maximum value in 2002; most of them were form Madrid, and only two cases presented animal contact. They were 11 boys and 7 girls, with a range of ages between 4 months and 9 years. Every patient had fever and some of them presented other symptoms such as asthenia and anorexia. The splenomegaly was the principal sign, followed by the pale skin and hepatomegaly. All of them presented anemia and some of them showed low blood platelets, leucopenia and high value of transaminasas and IgG. In every case the parasite could be seen in the bone marrow. 78% of them had positive antileishmania antibodies. The principal drug used within the treatment was the Antimoniato de Meglumina and in just one case Anfotericine B. Conclusions. The leishmaniasis is still a problem in our environment, affecting 1 to 3 years old children because of their immature immunodeficiency (AU)

Optimización de las condiciones de cultivo de las células mesenquimales de médula ósea humana para su uso en traumatología / Optimization of culture conditions of the human bone marrow mesenchymal stem cells for traumatology use

Las células mesenquimales (MSC) de la médula ósea(MO) humana constituyen un candidato celular muy prometedorpara regenerar el cartílago dañado. Las MSC generadasin vitro contienen dos poblaciones celulares condistinta capacidad de expansión y de diferenciación. En esteestudio, utilizando muestras de MO procedente de biopsiasde hueso, se definen las condiciones de cultivo quepermiten optimizar el rendimiento de los cultivos enriquecidosen células más pluripotentes. También se ha determinadoel contenido en células progenitoras de las MSC de laMO. Tras exposición a medios de diferenciación específicos,las MSC obtenidas en cultivo demostraron su capacidadosteogénica y condrogénica. Finalmente hemos demostradoque el plasma rico en plaquetas puede sustituiral factor de crecimiento transformante (TGF)-β1 utilizadopara inducir la condrogénesis no sólo en las MSC agregadasen micromasas, sino también en las crecidas en monocapay embebidas en un gel de fibrina

Mesenchymal stem cells (MSC) from human bone marrow(BM) represent a promising candidate cell type fordamaged cartilage repair. In vitro generated MSC containtwo cell populations with a distinct capability of expansionand differentiation. We have used BM samples derivedfrom human bone biopsies and we have defined cultureconditions for optimizing the yields of cultures enrichedfor pluripotent cells. Moreover, it has been determined thecontent of progenitor MSC in human BM. MSC could differentiateinto osteocytic and chondrocytic lineage afterculturing with defined culture mediums. Finally we demonstratedthat platelet-rich plasma can replace transforminggrowth factor (TGF)-β1 used to induce chondrogenicdifferentiation in MSC pelleted into micromasses but alsoin MSC cultured in monolayer and immersed in a fibrin gel

Capacidad regenerativa de las células de médula ósea autólogas después de un infarto agudo de miocardio / Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction

La insuficiencia cardíaca está considerada como la epidemia cardiovascular del siglo xxi. Su mortalidad y su morbilidad son muy elevadas y consumen cada vez más recursos sanitarios. Casi la mitad de los enfermos de insuficiencia cardíaca ha presentado un infarto de miocardio. El tratamiento de regeneración miocárdica con células madre ha surgido a principios de este siglo como una esperanza para el tratamiento de las enfermedades cardiovasculares. Los primeros estudios se han realizado en grupos pequeños de pacientes, pero los resultados indican cierto beneficio. El contexto del infarto agudo de miocardio es el más investigado en este campo. Para la evaluación de los resultados, la resonancia cardíaca se perfila como la herramienta más útil para el seguimiento de estos pacientes. Como toda técnica novedosa, también han surgido problemas de seguridad y, probablemente, en un futuro surgirán nuevas incógnitas, puesto que todavía hoy no conocemos el mecanismo de actuación de las células madre que trasplantamos o movilizamos hacia el corazón (AU)

Heart failure is considered the new cardiovascular epidemy of XXI century. Mortality and morbidity are very high, consuming more and more health resources. Most of these patients have suffered from a myocardial infarction. Stem cell therapy emerged at the beginning of this century as a new strategy for the treatment of cardiovascular diseases. The initial studies were done in small groups of patients showing benefits. Myocardial infarction is frequently investigated in this field. For the evaluation of these results magnetic resonance appears as a useful tool for the follow-up of these patients. As it usually happens with a new technique, safety problems have arisen and it is possible that in the near future new questions will arise as we still do not know how the progenitor cells we transplant or mobilize into the heart act (AU)

Regeneración de la retina a partir de células madre de la médula ósea / Retinal regeneration from bone marrow-derived stem cells

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Células estromales de la médula ósea: una fuente terapéutica alternativa en la restauración de enfermedades degenerativas del sistema nervioso central / Bone morrow stromal cells. An alternative source of restorative therapy in degenerative diseases of the central nervous system

Objetivo. Demostrar las capacidades de las células de la médula ósea para limitar o desacelerar el daño y la degeneración neuronal crónica que se producen en las enfermedades degenerativas del sistema nervioso central (SNC), además de la potencialidad del método para suministrar otras sustancias o material genético. Desarrollo. La búsqueda de nuevas fuentes de células que conserven la capacidad de dividirse y diferenciarse hacia distintos fenotipos celulares, abre enormes oportunidades en el tratamiento restaurador de estas entidades. En este sentido, las células de la médula ósea, especialmente las células madre estromales, han demostrado que conservan un alto potencial de diferenciación para originar distintas estirpes celulares características del cerebro (neuronas, astrocitos y glías), así como la capacidad de restablecer la población de células madre cuando se estimulan adecuadamente. Conclusiones. Los futuros estudios experimentales tendrán como propósito la búsqueda de nuevas vías para mejorar la composición, viabilidad y diferenciación de las células que se implanten y evaluarán su efecto sobre las enfermedades del SNC (AU)

Aims. The aim of this study is to describe the capacity of bone marrow cells to limit or slow down the damage and chronic neuronal degeneration produced by degenerative diseases of the central nervous system (CNS), as well as the potential capacity of the method to provide other substances or genetic material. Development. The search for new sources of cells that maintain the ability to divide and distinguish themselves from different cellular phenotypes opens up huge new opportunities in the restorative therapy of these clinical entities. Bone marrow cells, and especially stromal stem cells, have been seen to conserve a high capacity to distinguish and originate different strains of characteristic brain cells (neurons, astrocytes, and glial cells), and also the capacity to restore the population of stem cells when they are stimulated in a suitable fashion. Conclusions. Future experimental studies will be aimed at searching for new ways to enhance the composition, viability and differentiation of the cells to be implanted and will evaluate their effects on diseases of the CNS (AU)