“Is it Time for Reviewer 3 to Request Human Organ Chip Experiments Instead of Animal Studies?”
Dr. Donald Ingber, Director of the Wyss Institute for Biologically Inspired Engineering at Harvard University, wrote this controversially titled Report last year. It was based on the often remarked observation that reviewers ask for animal studies respective of their physiological relevance. We can answer this deceptively simple question by delving into the nuance of any
research. In many cases, researchers are probing cellular, tissue, or organ-level mechanisms of disease. Organ chips, with their defined composition and the ability to tweak many parameters, can provide an unprecedented window into the organ-level mechanisms which many animal models may fail to provide. In these cases, using animal models, modified to mimic phenotypes of human disease, purely for the sake of historical precedent may backfire.
However, we are still on the path to perfecting various microphysiological systems (MPS) models. Some of the key challenges include mimicking human cognition and neurogenesis, biological clock, response to pathogens, and systemic behaviors in vitro. We discuss a few recent studies that come close to recapitulating these challenging areas in MPS models
In addition to recreating human organs in vitro, another branch of
technology that is helping to understand human biology has been
advanced bio-imaging tools that visualize and measure human cell biology, biochemistry, and physiology in a non-invasive manner. We discuss a new study that has to build a new imaging tool that can image entire intact human organs. Information from such tools could contribute immensely to the global efforts that are attempting to map every cell in the human body.
In this newsletter, we have tried to cover recent and exciting studies that have thrown light on many critical considerations of microphysiological systems models. We hope you find it equally insightful and enjoy going through it!
Surat Parvatam, PhD
Senior Research Associate,
Centre for Predictive Human Model Systems, AIC-CCMB
Dr. Biman Mandal, Professor, IIT Guwahati
The webinar focussed on how to build a 3D printed osteoarthritic/osteochondral biomimetic model as a high throughput anti-inflammatory drug screening platform. Osteochondrosis is a degenerative disease currently without a cure. This platform was built using a polymer-based on silk from Bombyx Mori. It has an RGD motif which allows it to bind to the cells and prevent osteoproliferation. This biopolymer was used as a scaffold to build a 3D tissue model and test prospective therapeutic molecules.
Dr. Uday Saxena, Co-founder Reagene Biosciences
Dr Uday Saxena spoke about a 3D-printed human vascular lung developed by his research group to study COVID-19 infection. This in vitro lung model could capture critical elements of disease pathogenesis, including entry of the virus, binding to ACE2 receptors, cytokine storm, thrombosis and inflammation. In addition, in silico drug screening was performed to screen drugs which can be repurposed for COVID-19 infection. Based on the results, Ertugliflozin, Tyrosine Kinase Inhibitors, Homoharrin getonine were three molecules which were identified as potential molecules which could help in combating COVID 19.
Dr. Prajakta Dandekar, Assistant Professor, ICT Mumbai
Dr Dandekar spoke about different methods of 3D cell culture, such as spheroids, scaffold free approaches, magnetic levitation, hydrogen culture, nanofibers, bioprinting and organ on chips. Currently her lab is working various on vitro models systems, including nanofibrous dressing for wound healing, freeze-dried scaffolds for skin tissue engineering, spheroidbased models for lung cancer and retina, bioprinted skin. To increase the physiological relevance and flow conditions observed in vivo, they are also currently working on skin & retinaon-chip models. This model combines the advantages of 3D cell culture, perfusion, and microfluidic technology.