Mesenchymal Stem Cell-Derived Extracellular Vesicles: New Soldiers in the War on Immune-Mediated Diseases.

Inflammatory diseases are a group of debilitating disorders with varying degrees of long-lasting functional impairment of targeted system. New therapeutic agents that will attenuate on-going inflammation and, at the same time, promote regeneration of injured organ are urgently needed for the treatment of autoimmune and inflammatory disorders. During the last decade numerous studies have demonstrated that crucial therapeutic benefits of mesenchymal stem cells (MSCs) in inflammatory diseases are based on the effects of MSC-produced paracrine mediators and not on the activity of engrafted cells themselves. Thus, to overcome the limitations of stem cell transplantation, MSC-derived extracellular vesicles (MSC-EVs) have been rigorously investigated, as a promising cell-free pharmaceutical component. In this review, we focus on the mechanisms of MSC-EV covering the current knowledge on their potential therapeutic applications for immune-mediated diseases.

Scaling up human mesenchymal stem cell manufacturing using bioreactors for clinical uses.

Human mesenchymal stem cells (hMSCs) are multipotent cells and an attractive therapeutic agent in regenerative medicine and intensive clinical research. Despite the great potential, the limitation that needs to be overcome is the necessity of ex vivo expansion because of insufficient number of hMSCs presented within adult organs and the high doses required for a transplantation. As a result, numerous research studies aim to provide novel expansion methods in order to achieve appropriate numbers of cells with preserved therapeutic quality. Bioreactor-based cell expansion provide high-level production of hMSCs in accordance with good manufacturing practice (GMP) and quality standards. This review summarizes current knowledge about the hMSCs manufacturing platforms with a main focus to the application of bioreactors for large-scale production of GMP-grade hMSCs.

Interrogating and Quantifying In Vitro Cancer Drug Pharmacodynamics via Agent-Based and Bayesian Monte Carlo Modelling.

The effectiveness of chemotherapy in cancer cell regression is often limited by drug resistance, toxicity, and neoplasia heterogeneity. However, due to the significant complexities entailed by the many cancer growth processes, predicting the impact of interference and symmetry-breaking mechanisms is a difficult problem. To quantify and understand more about cancer drug pharmacodynamics, we combine in vitro with in silico cancer models. The anti-proliferative action of selected cytostatics is interrogated on human colorectal and breast adenocarcinoma cells, while an agent-based computational model is employed to reproduce experiments and shed light on the main therapeutic mechanisms of each chemotherapeutic agent. Multiple drug administration scenarios on each cancer cell line are simulated by varying the drug concentration, while a Bayesian-based method for model parameter optimisation is employed. Our proposed procedure of combining in vitro cancer drug screening with an in silico agent-based model successfully reproduces the impact of chemotherapeutic drugs in cancer growth behaviour, while the mechanisms of action of each drug are characterised through model-derived probabilities of cell apoptosis and division. We suggest that our approach could form the basis for the prospective generation of experimentally-derived and model-optimised pharmacological variables towards personalised cancer therapy.