Anti-cancer drug validation: the contribution of tissue engineered models

Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio

Development and application of human adult stem or progenitor cell organoids

Adult stem or progenitor cell organoids are 3D adult-organ-derived epithelial structures that contain self-renewing and organ-specific stem or progenitor cells as well as differentiated cells. This organoid culture system was first established in murine intestine and subsequently developed for several other organs and translated to humans. Organoid cultures have proved valuable for basic research and for the study of healthy tissue homeostasis and the biology of disease. In addition, data from proof-of-principle experiments support promising clinical applications of adult stem or progenitor cell organoids. Although renal organoids have many potential applications, an adult stem or progenitor cell organoid culture system has not yet been developed for the kidney. The development of such a system is likely to be challenging because of the intricate renal architecture. Differentiated 3D cultures and stem or progenitor cell 3D sphere cultures are, however, available for the kidney. These cultures indicate the feasibility of renal organoid culture and provide a solid basis for its development. In this Review, we discuss the state-of-the-art of human adult stem or progenitor cell organoid culture and the potential of renal organoids as tools in basic and clinical research