The use of multipotent mesenchymal stromal cells (MSCs) as candidate medicines for treating a variety of pathologies is based on their qualities as either progenitors for the regeneration of damaged tissue or producers of a number of molecules with pharmacological properties. Preclinical product development programmes include the use of well characterized cell populations for proof of efficacy and safety studies before testing in humans. In the field of orthopaedics, an increasing number of translational studies use sheep as an in vivo test system because of the similarities with humans in size and musculoskeletal architecture. However, robust and reproducible methods for the isolation, expansion, manipulation and characterization of ovine MSCs have not yet been standardised. The present study describes a method for isolation and expansion of fibroblastic-like, adherent ovine MSCs that express CD44, CD90, CD140a, CD105 and CD166, and display trilineage differentiation potential. The 3-week bioprocess proposed here typically yielded cell densities of 1.4 × 10 MSCs/cm at passage 2, with an expansion factor of 37.8 and approximately eight cumulative population doublings. The osteogenic potential of MSCs derived following this methodology was further evaluated in vivo in a translational model of osteonecrosis of the femoral head, in which the persistence of grafted cells in the host tissue and their lineage commitment into osteoblasts and osteocytes was demonstrated by tracking enhanced green fluorescent protein-labelled cells. Copyright © 2016 John Wiley & Sons, Ltd.

In the field of orthopedics, translational research of novel therapeutic approaches involves the use of large animal models (such as sheep, goat, pig, dog, and horse) due to the similarities with humans in weight, size, joint structure, and bone/cartilage healing mechanisms. Particularly in the development of cell-based therapies, the lack of manageable immunocompromised preclinical large animal models prevents the use of human cells, which makes it necessary to produce equivalent homologous cell types for the study of their pharmacodynamics, pharmacokinetics, and toxicology. The methods described herein allow for the isolation, expansion, manipulation, and characterization of fibroblastic-like ovine bone marrow-derived multipotent mesenchymal stromal cells (BM-MSC) that, similar to human BM-MSC, adhere to standard plastic surfaces; express specific surface markers such as CD44, CD90, CD140a, CD105, and CD166; and display trilineage differentiation potential in vitro. Homogeneous cell cultures result from a 3-week bioprocess yielding cell densities in the range of 2-4 × 10 MSC/cm at passage 2, which corresponds to ∼8 cumulative population doublings. Large quantities of BM-MSC resulting from following this methodology can be readily used in proof of efficacy and safety studies in the preclinical development stage. © 2018 by John Wiley & Sons, Inc.

Este libro versa sobre un grupo de ensayos de corte humanista realizados por un grupo selecto de profesionales de diferentes países, Cuba, México, Ecuador, Argentina y los Estados Unidos. Todos, de manera unánime, coincidieron en escribir sobre el papel de la humanística en la enseñanza de las ciencias, en su sentido más general, en la importancia que la misma tiene en la formación de conductas, valores y actitudes en los estudiantes y todas aquellas personas que, como seres humanos, necesitan de ese humanismo tan necesario en nuestros días. La Humanística que usted podrá leer en este material es parte del Pensamiento Profesoral Pedagógico (3P) desarrollado por docentes que han estado en el aula durante un período de tiempo estimable como para que sus aportes, tomando en consideración sus experiencias, sean reconocidos esenciales en el trabajo que día a día se desarrolla en las instituciones educativas en todos sus niveles.

Background Proper bony tissue regeneration requires mechanical stabilization, an osteogenic biological activity and appropriate scaffolds. The latter two elements can be combined in a hydrogel format for effective delivery, so it can readily adapt to the architecture of the defect. Results We evaluated a Good Manufacturing Practice-compliant formulation composed of bone marrow-derived mesenchymal stromal cells in combination with bone particles (Ø = 0.25 to 1 µm) and fibrin, which can be readily translated into the clinical setting for the treatment of bone defects, as an alternative to bone tissue autografts. Remarkably, cells survived with unaltered phenotype (CD73 + , CD90 + , CD105 + , CD31 - , CD45 - ) and retained their osteogenic capacity up to 48 h after being combined with hydrogel and bone particles, thus demonstrating the stability of their identity and potency. Moreover, in a subchronic toxicity in vivo study, no toxicity was observed upon subcutaneous administration in athymic mice and signs of osteogenesis and vascularization were detected two months after administration. Conclusions The preclinical data gathered in the present work, in compliance with current quality and regulatory requirements, demonstrated the feasibility of formulating an osteogenic cell-based tissue engineering product with a defined profile including identity, purity and potency ( in vitro and in vivo ), which is required prior to move towards its use of prior to its clinical use.

A813independent reviewers performed the evaluation and a third reviewer or concession resolved any disagreement. The quality of Budget Impact Analyses on Drugs was evaluated according to Principles of Good Practice BIA -ISPOR 2012 Results: Publications were found between 2001 and 2015. More than 70% published since 2010. USA, Spain, Italy and UK together produced more than 50% of the publications. More than 70% did not declare a guideline used (even after the year 2010). The most usually guideline (14%) was the ISPOR (after the year 2009). Even guideline being used the studies did not present all the requirements. More than 30% analysis were just a projection of expenditures. More than 42% did not use reference scenario. More than 30% used smaller horizon time than three years. More than 50% of the study perspective the public system. More than 50% of the analyses were performed by statistical method using a spreadsheet. More than 21% did not do sensitivity analysis. More than 90% did not present model validation. More than 80% of the studies report limitations in the methods. Only 19% of the studies declare no conflicts of interest. ConClusions: The amount of budget impact analysis has increased, but few studies have yet been carried out based on guidelines and registers all the requirements. Many methodological uncertainties were identified and most of the studies recorded conflict of interest. The budget impact analysis still lack acceptable quality.

Las historias que pueden leerse en este libro tienen, como eje común, la concatenación universal de los fenómenos en las diferentes esferas de la realidad. En cada historia se muestra la conexión entre cada aspecto tratado y entre todas las historias ocurre exactamente lo mismo. El objetivo central es que el lector se apropie de la idea de que el mundo es integrado y que nada puede analizarse por partes aisladas, porque jamás se llegaría a la esencia del todo. Como Einstein, los autores de este libro consideran que la ciencia es parte de la unidad, y si esta se baña de humanismo, mucho mejor.