Promethera Biosciences (Belgium)

Triply periodic minimal surfaces (TPMSs) are relevant structures for building synthetic bone grafts due to their tortuosity and interconnected pores. In order to investigate their porosity and mechanical properties, three different hydroxyapatite-based TPMSs were printed by vat polymerization: the Schwartz diamond, Schwartz primitive, and gyroid scaffolds. Each structure was designed with three levels of porosity, two different pore sizes, and two different wall thicknesses so as to gain an understanding of the effect of pore size and wall thickness on the mechanical properties. The results highlighted the importance of cleaning in the manufacturing process and its impact on the final porosity, especially for small pore sizes. This article intends to be among the first to discuss mechanical testing with macro spherical indentation. Bending and macro spherical indentation resistance tests revealed differences in the mechanical properties between the different structures, with a strong sensitivity of bending strength to the presence of cracks after thermal treatment. Notably, increasing the wall thickness was shown to increase the risk of damage to the solid parts of the scaffolds, therefore lowering the bending strength.

The efficacy of mesenchymal stem cell infusion is currently tested in numerous clinical trials. However, therapy-induced thrombotic consequences have been reported in several patients. The aim of this study was to optimize protocols for heterologous human adult liver-derived progenitor cell (HHALPC) infusion, in order to eliminate acute thrombogenesis in liver-based metabolic or acute decompensated cirrhotic (ADC) patients. In rats, thrombotic effects were absent when HHALPCs were infused at low cell dose (5 × 106 cells/kg), or at high cell dose (5 × 107 cells/kg) when combined with anticoagulants. When HHALPCs were exposed to human blood in a whole blood perfusion assay, blocking of the tissue factor (TF) coagulation pathway suppressed fibrin generation and platelet activation. In a Chandler tubing loop model, HHALPCs induced less explosive activation of coagulation with blood from ADC patients, when compared to blood from healthy controls, without alterations in coagulation factor levels other than fibrinogen. These studies confirm a link between TF and thrombogenesis, when TF-expressing cells are exposed to human blood. This phenomenon however, could be controlled using either a low, or a high cell dose combined with anticoagulants. In clinical practice, this points to the suitability of a low HHALPC dose infusion to cirrhotic patients, provided that platelet and fibrinogen levels are monitored.

The Tissue Engineering & Regenerative Medicine International Society-Europe (TERMIS-EU) Industry Committee as well as its TERMIS-Americas (AM) counterpart intend to address the specific challenges and needs facing the industry in translating academic research into commercial products. Over the last 3 years, the TERMIS-EU Industry Committee has worked with commercial bodies to deliver programs that encourage academics to liaise with industry in proactive collaborations. The TERMIS-EU 2013 Industry Symposium aimed to build on this commercial agenda by focusing on two topics: Operations Management (How to move a process into the good manufacturing practice [GMP] environment) and Clinical Translation (Moving a GMP process into robust trials). These topics were introduced by providing the synergistic business perspective of partnering between the multiple regenerative medicine stakeholders, throughout the life cycle of product development. Seven industry leaders were invited to share their experience, expertise, and strategies. Due to the complex nature of regenerative medicine products, partnering for their successful commercial development seems inevitable to overcome all obstacles by sharing experiences and expertise of all stakeholders. When ideally implemented, the "innovation quotient" of a virtual team resulting from the combination of internal and external project teams can be maximized through maximizing the three main dimensions: core competences, technology portfolio, and alliance management.

Promethera Biosciences (Mont-St-Guibert, BE) is developing cell therapies to treat several liver genetic metabolic diseases, such as the Crigler-Najjar syndrome. Human heterologous adult liver progenitors cells (HHALPCs) were initially cultivated in 2D standard cultivation devices. The present study is investigating the feasibility to cultivate HHALPCs in Xpansion bioreactors, with the following objectives: ➢ The process must be closed ➢ The growth rate and population-doubling level (i.e. the number of times the cells in the population has doubled) must be at least equivalent to the current process in multilayer trays ➢ The process must comply to the cGMP rules ➢ The cells must succeed the quality control (QC) test specifications at the end of cultivation, i.e. cells must remain undifferentiated and show the presence of HHAPLCs markers, while exhibiting the capacity to differentiate toward functional hepatocytes. Integrity® Xpansion™ multiplate bioreactors have been specifically designed to enable an easy transfer from existing multiple-tray-stack processes by offering the same cell growth environment on 2-D hydrophylized Polystyrene (PS) plates in a fully closed system. To make the bioreactors compact, the headspace between each plate has been reduced to a minimum (1.3 mm). Gas transfer is made through a semi-permeable silicone tubing mounted in the central column. Additionally, critical cell culture parameters such as pH and DO are controlled and the cell density is automatically monitored via a specific holographic microscope developed by Ovizio