Addressing the Manufacturing Challenges of Cell-Based Therapies.

Exciting developments in the cell therapy field over the last decades have led to an increasing number of clinical trials and the first cell products receiving marketing authorization. In spite of substantial progress in the field, manufacturing of cell-based therapies presents multiple challenges that need to be addressed in order to assure the development of safe, efficacious, and cost-effective cell therapies.The manufacturing process of cell-based therapies generally requires tissue collection, cell isolation, culture and expansion (upstream processing), cell harvest, separation and purification (downstream processing), and, finally, product formulation and storage. Each one of these stages presents significant challenges that have been the focus of study over the years, leading to innovative and groundbreaking technological advances, as discussed throughout this chapter.Delivery of cell-based therapies relies on defining product targets while controlling process variable impact on cellular features. Moreover, commercial viability is a critical issue that has had damaging consequences for some therapies. Implementation of cost-effectiveness measures facilitates healthy process development, potentially being able to influence end product pricing.Although cell-based therapies represent a new level in bioprocessing complexity in every manufacturing stage, they also show unprecedented levels of therapeutic potential, already radically changing the landscape of medical care.

Blocking negative effects of senescence in human skin fibroblasts with a plant extract.

There is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life- and healthspan of mice. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). Here we identified an extract from the plant Solidago virgaurea subsp. alpestris, which exhibited weak senolytic activity, delayed the acquisition of a senescent phenotype and induced a papillary phenotype with improved functionality in human dermal fibroblasts. When administered to stress-induced premature senescent fibroblasts, this extract changed their global mRNA expression profile and particularly reduced the expression of various SASP components, thereby ameliorating the negative influence on nearby cells. Thus, the investigated plant extract represents a promising possibility to block age-related loss of tissue functionality.