The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

Growth patterns in early childhood and the onset of menarche before age twelve Patrones de crecimiento en la infancia precoz y ocurrencia de menarca antes de doce años de edad Padrões de crescimento na infância precoce e ocorrência de menarca antes de doze anos de idade

OBJECTIVE: To examine the relationship between growth patterns in early childhood and the onset of menarche before age 12. METHODS: The study included 2,083 women from a birth cohort study conducted in the city of Pelotas, Southern Brazil, starting in 1982. Anthropometric, behavioral, and pregnancy-related variables were collected through home interviews. Statistical analyses were performed using Pearson's chi-square and chi-square test for linear trends. A multivariable analysis was carried out using Poisson regression based on a hierarchical model. RESULTS: Mean age of menarche was 12.4 years old and the prevalence of menarche before age 12 was 24.3%. Higher weight-for-age, height-for-age, and weight-for-height z-scores at 19.4 and 43.1 months of age were associated with linear tendencies of increased prevalence and relative risks of the onset of menarche before age 12. Girls who experienced rapid growth in weight-for-age z-score from birth to 19.4 months of age and in weight-for-age or height-for-age z-scores from 19.4 to 43.1 months of age also showed higher risk of menarche before age 12. Higher risk was seen when rapid growth in weight-for-age z-score was seen during these age intervals and the highest risk was found among those in the first tertile of Williams' curve at birth. Rapid growth in weight-for-height z-score was not associated with menarche before age 12. CONCLUSIONS: Menarche is affected by nutritional status and growth patterns during early childhood. Preventing overweight and obesity during early childhood and keeping a "normal" growth pattern seem crucial for the prevention of health conditions during adulthood.<br>OBJETIVO: Evaluar la relación entre patrones de crecimiento en la infancia precoz y ocurrencia de menarca antes de 12 años de edad. MÉTODOS: El estudio incluyó 2.083 mujeres del estudio de cohorte de nacidos en Pelotas, 1982, Sur de Brasil. Variables antropométricas, comportamentales y relacionadas a la gestación fueron colectadas por medio de entrevistas domiciliares. Los análisis estadísticos empleados fueron el chi-cuadrado de Pearson y ji-cuadrado para tendencia linear. Así mismo, análisis multivariable fue realizado usando la regresión de Poisson, siguiendo un modelo jerárquico. RESULTADOS: El promedio de edad de menarca fue de 12,4 años y la prevalencia de menarca antes de los 12 años fue de 24,3%. Mayores valores de escores Z en los índices peso/edad, altura/edad y peso/altura a los 19,4 y 43,1 meses correspondieron a mayores riesgos de presentar menarca antes de los 12 años. Ese riesgo fue sistemáticamente mayor en la edad de 43,1 meses. Niñas que experimentaron rápido crecimiento en escore Z de peso/edad entre el nacimiento y 19,4 meses o en escore Z de peso/edad o altura/edad entre 19,4 y 43,1 meses, mostraron mayores riesgos. El riesgo de menarca antes de los 12 años fue más elevado cuando el crecimiento rápido en escore Z de peso/edad ocurrió en ambos períodos; y aún mayor entre las niñas del primer tercil de la curva de Williams. Crecimiento rápido en escore Z de peso/altura no estuvo asociado con menarca antes de los 12 años. CONCLUSIONES: La edad de menarca se mostró influenciada por el estado nutricional y patrones de crecimiento durante la infancia precoz. Así, evitar sobrepeso y obesidad en la infancia precoz manteniendo un patrón "normal" de crecimiento parece ser importante para prevenir problemas de salud en futuras etapas de vida.<br>OBJETIVO: Avaliar a relação entre padrões de crescimento na infância precoce e ocorrência de menarca antes de 12 anos de idade. MÉTODOS: O estudo incluiu 2.083 mulheres do estudo de coorte de nascidos em Pelotas, RS, de 1982. Variáveis antropométricas, comportamentais e relacionadas à gestação foram coletadas por meio de entrevistas domiciliares. As análises estatísticas empregadas foram o qui-quadrado de Pearson e qui-quadrado para tendência linear. Além disso, análise multivariável foi realizada usando a regressão de Poisson, seguindo um modelo hierárquico. RESULTADOS: A média de idade da menarca foi de 12,4 anos e a prevalência de menarca antes dos 12 anos foi de 24,3%. Maiores valores de escores Z nos índices peso/idade, altura/idade e peso/altura aos 19,4 e 43,1 meses corresponderam a maiores riscos de apresentar menarca antes dos 12 anos. Esse risco foi sistematicamente maior na idade de 43,1 meses. Meninas que experimentaram rápido crescimento em escore Z de peso/idade entre o nascimento e 19,4 meses ou em escore Z de peso/idade ou altura/idade entre 19,4 e 43,1 meses, mostraram os maiores riscos. O risco de menarca antes dos 12 anos foi mais elevado quando o crescimento rápido em escore Z de peso/idade ocorreu em ambos os períodos; e ainda maior entre as meninas do primeiro tercil da curva de Williams. Crescimento rápido em escore Z de peso/altura não esteve associado com menarca antes dos 12 anos. CONCLUSÕES: A idade da menarca mostrou-se influenciada pelo estado nutricional e padrões de crescimento durante a infância precoce. Assim, evitar sobrepeso e obesidade na infância precoce mantendo um padrão "normal" de crescimento parece ser importante para prevenir problemas de saúde em futuras etapas da vida

Genetic determinants of cerebral vasospasm, delayed cerebral ischemia, and outcome after aneurysmal subarachnoid hemorrhage

Despite extensive effort to elucidate the cellular and molecular bases for delayed cerebral injury after aneurysmal subarachnoid hemorrhage (aSAH), the pathophysiology of these events remains poorly understood. Recently, much work has focused on evaluating the genetic underpinnings of various diseases in an effort to delineate the contribution of specific molecular pathways as well as to uncover novel mechanisms. The majority of subarachnoid hemorrhage genetic research has focused on gene expression and linkage studies of these markers as they relate to the development of intracranial aneurysms and their subsequent rupture. Far less work has centered on the genetic determinants of cerebral vasospasm, the predisposition to delayed cerebral injury, and the determinants of ensuing functional outcome after aSAH. The suspected genes are diverse and encompass multiple functional systems including fibrinolysis, inflammation, vascular reactivity, and neuronal repair. To this end, we present a systematic review of 21 studies suggesting a genetic basis for clinical outcome after aSAH, with a special emphasis on the pathogenesis of cerebral vasospasm and delayed cerebral ischemia. In addition, we highlight potential pitfalls in the interpretation of genetic association studies, and call for uniformity of design of larger multicenter studies in the future