Challenges in developing an off-the-shelf cell therapy for ACLF and NASH

ConclusionThe dosing for this indication is likely to be in the order of 100 million cells per infusion. Large numbers of cells thus need to be manufactured and using standard cell culture techniques would make it too expensive and labour intensive. A standard expansion protocol in flasks or cell factories is an open process, and therefore run in expensive clean rooms to avoid the risk of contamination. We have explored several state-of-the art-bioreactor systems, and various types of microcarriers in stirred tanks from different manufacturers. We have tested these systems to optimize the complete workflow of HepaStem culture, including stem cell isolation from livers and expansion up to the scale of many clinical doses. Quality control and comparability studies were performed to verify that the characteristics of HepaStem cells harvested from the different procedures were maintained. We have built a production platform, almost entirely in closed system, that can provide the large numbers of clinical doses that would be needed for the treatment of NASH. This platform functions with a strong reduction of human labour and it also modular and flexible to anticipate growing demand. In parallel we have developed serum-free and xenofree culture methods to be able to abandon the use of animal-derived products, for the related risks and because animal sera become scarce and expensive.
Source: Cytotherapy - Category: Cytology Source Type: research