19 July 2019

This edition of research round-up reports on very different aspects of applying human-focused technologies and strategies.  The paper by Velasco et al. entitled ”Individual brain organoids reproducibly form cell diversity of the human cerebral cortex” and published in Nature shows that results obtained from brain organoids are reliable and can be replicated.  In their paper ”Phosphorylation of SOCS1 inhibits the SOCS1-p53 tumor suppressor axis” published in Cancer Research, Ferbeyre et al. unveil the molecular mechanisms that turn a tumor suppression gene into an oncogene and suggest that an FDA-approved drug may stop this oncogene. Lastly, the study “Hyperphysiological compression of articular cartilage induces an osteoarthritic phenotype in a cartilage-on-a-chip” published in Nature Biomedical Engineering by Occhetta et al. reports on the development of a human cartilage-on-a-chip to be used for screening new drugs for Osteoarthritis.

Reliable 3D brain organoids

Embryonic brain development is essentially the same for every one of us- the same regions are formed, made up of the same cell types carrying out the same functions.  Models of the human brain have been under development for many years, with increasing sophistication, such that we are now accustomed to reading about three dimensional, multi-cellular organoids and spheroids that exhibit increasing developmental maturity – but creating different models in different labs with different protocols has issues of its own. Besides the fact that animal data is not translatable to humans and that animals are poor models for human diseases, there is a reproducibility crisis in animal research –  and research employing purely in vitro methods may not be far behind. For models that employ induced pluripotent stem cells (iPSC), it is crucial that researchers fully describe the differentiation protocol adopted – to ensure confidence in the cell type under test but also to permit the rigorous replicate studies that are necessary to advance the research. [Read more…]

7 July 2019

A new article published in the journal Frontiers in Cellular and Infection Microbiology shows that research built around human-mimetic tools are more likely to succeed in the search for effective treatments for and prevention of flavivirus infection as compared to research using monkeys or other animals as laboratory models. The study, led by Dr. David Pamies at the University of Lausanne (formerly of the Johns Hopkins Center for Alternatives to Animal Testing), with researchers at Johns Hopkins University and the National Institute of Allergy and Infectious Diseases’ Vaccines Research Center in the U.S., carried out a comprehensive review of the models used to study deadly mosquito-borne flaviviruses (MBF) such as dengue fever and the Zika virus, known to cause neurological disease in humans.

The authors report that the host specificity of viral diseases presents a challenge for studying these human viruses in animals. Vaccines that had proved successful in primate tests have failed in human trials, leading to intense research using knockout and humanized transgenic mice. Thus, human genes relevant to the capacity of the virus to infect humans have been inserted into mice, but these modified animals are still mice, and the authors recognize drawbacks to this approach: “… several factors are recognized to influence the susceptibility of mice to MBF infection that limit applicability to humans.” For example, mice fail to display human disease symptoms if bitten by an infected mosquito (the human route of infection), and the mouse immune response varies depending on the animal’s age. Furthermore, the experiments are not reproducible in different laboratories – often an issue in animal experiments. [Read more…]

25 April 2019

Atal Incubation Centre (AIC) at the Centre for Cellular and Molecular Biology (CCMB), in collaboration with Humane Society International/ India (HSI/India), has launched the Centre for Predictive Human Model Systems, a centre dedicated to enable a paradigm shift in science by focusing on 21^st century new approach methodologies instead of animal models. The centre aims to prioritize investment in human-based, non-animal methodologies in life sciences research in India. This will be done by establishing a multi – stakeholder think-tank that represents the growing body of expertise on new approach methodologies on a scientific and policy level. Keeping in mind the 21^st century biomedical science and toxicology motive globally to break siloes and forge partnerships among the scientific community for better flow of knowledge, support for research and open-access publication of literature will be a focus of the centre.

“This centre is a natural alignment to AIC’s objective of supporting new innovation and technologies. This sector of predictive human biology is ripe for investment and I am certain that this partnership with HSI/India will kindle the much-needed investment in this field,” said Dr Madhusudan Rao, CEO of AIC – CCMB. [Read more…]