Use of Organoids in Medicinal Chemistry: Challenges on Ethics and Biosecurity

Abstract

Organoids: applicationsOrganoids are three-dimensional (3D) multicellular stem-cell-derived systems comprising organ-specific cell types, that exhibit key structural and functional properties of a variety of specific organs [1]; this technology has been chosen by Nature Methods as Method of the Year 2017 for the fascinating potential as tool to probe human biology and disease.Organoids can be grown from pluripotent stem cells, embryonic stem cells, induced pluripotent stem cells and from organ-restricted adult stem cells. These cells differentiate in a controlled fashion in specific growth factors and culture media, with the support of a 3D matrix which allows cell growth, orientation and stratification. The resulting organoids replicate the development, metabolism, architecture and physiology of the real organ [2]. In fact, unlike in vitro traditional 2D cultures, organoids are formed by genomic stable, self-renewing and self-organizing stem cell-derived populations of differentiated cells that exhibit similar composition (they comprise all major cell lineages at frequencies similar to those in living tissue) and similar organ architecture and functionality as the tissue of origin. The technique allows expansions of tissue-specific stem cells and their differentiated progeny. Starting from very small amounts of material (such as biopsies); organoids can be expanded indefinitely, cryopreserved as biobanks and easily manipulated using techniques similar to those used for traditional 2D cell cultures [3]. Organoids are of course more physiologically relevant than traditional cell culture models and are easier to manipulate and study than in vivo mouse/human models. Gene-editing technologies can be used to produce and even self-transplant repaired, healthy organoids from patients with genetic defects.In the last years, human organoids have been established for a wide range of organs, including salivary gland, esophagus, stomach, pancreas, liver, intestine, colon, kidney, prostate, lung, retina and brain. Using organoids, many types of human diseases have been modeled, ranging from Barrett's esophagus to Helicobacter pylori infection, cystic fibrosis, inflammatory bowel disease, bacterial or viral infections and even autism [3]. The luminal epithelia of human gastric organoids are efficiently colonized by Helicobacter pylori (the bacterium identified as the major cause of gastritis and one of the major agents of gastric cancer onset) and relevant physiological changes were demonstrated in this setting, including an increase in proliferation due to oncogenic CagA and increased β-catenin signaling [4]. Further, renal organoids have been used for the study of infections caused by Shiga-toxin-producing Escherichia coli [5]; these types of studies are yielding important contributions in understanding the pathogenic mechanisms of infections and are used to improve the strategies of treatment.Many cancer models have been studied using organoids from glioblastoma, colorectal, gastrointestinal, pancreatic, prostate, breast, b...

What can biofabrication do for space and what can space do for biofabrication?

“…Reducing uncertainties and, if possible, filling knowledge gaps are both scientific and ethical obligations. Furthermore, debates are taking place about the potential costs, the use of stem cells, the risks of misuse, and experiments on the human body [91,92].…”

Role of three-dimensional printing and artificial intelligence in the management of hepatocellular carcinoma: Challenges and opportunities

“…Another concern is obtaining genuine informed consent. For the patients donating, before consenting, the patients’ autonomy and control over their biological condition should be established, and concerns regarding anonymity, data protection, future claims on their donated tissues, as well as these tissues intended short-term and long-term use should be addressed[ 169 , 171 ]. Similarly, before giving informed consent, transplanted patients’ concerns regarding safety, short-term and long-term risks, the uncertainty involved, and potential unknown consequences should be addressed.…”

“…To add to this concern, when 3D bioprinting is advanced enough to produce organs that are superior in certain aspects compared to human organs, 3D bioprinting technologies could be used for eugenic purposes[ 172 ]. With steadily decreasing prices and steadily increasing availability, there is an actual concern about unregulated 3D bioprinting research that could be used for malignant purposes, including bioterrorism[ 171 ]. Evidently, there is a need for a robust regulatory framework to address all these emerging concerns, which could be obtained by elaborating on our existing ethical and regulatory standards as encompassed in the Helsinki Declaration, the Oviedo Convention system, and UN’s Declaration on Human Rights.…”

Ethical Challenges in Organoid Use

“…Rinaldi and Colotti argue that organoids can be used for harmful purposes and bioterrorism. For instance, lung and brain organoids could be used to test the toxicity of new chemical weapons, toxic chemicals or toxins, or to assess the infectivity of biological agents [ 50 ]. More than other in vitro cell systems, the knowledge gained through the use of organoids can also be used for military applications.…”