Editor’s Note: What is common between the legendary movies Star Wars and Blade Runner? The most probable answer would be Mr. Harrison Ford. However, being years ahead of their time, both these movies introduced the transforming concept of being artificial in their unique ways. The R2D2 and C3PO versions of artificial intelligence from Star Wars are a reality now with our Mars Rovers and Amazon Echoes. But what about the concept of artificial organs, courtesy Blade Runner. More than 35 years later, we know that shopping for genetically identical, replacement body parts remains the stuff of science fiction. The last decade, however, has witnessed the first steps in the creation of miniaturised version of these body parts. In this Medness blog from #ClubSciWri, Heena Khatter assembles the stories of science, entrepreneurship and the market of artificial organogenesis stemming from 3D Cultures, that will redefine the precision of future medicine.– Abhinav Dey
What is 3D culture?
3D cell cultures create a physiologically relevant artificial environment for growth of cells. They have gained popularity in the past few years, as they mimic the in-vivo conditions better than 2D cultures in petri dishes- which have been used for decades for growing cells. The culture methods are broadly divided into scaffold and scaffold-free.
- In-vivo cells are surrounded by an extra-cellular matrix and a milieu of nutrients. The scaffold serves as a support and provides the microenvironment for cellular growth. Commonly used scaffolds range from polymers, hydrogels derived from natural sources (collagen, laminin, and gelatin) to micropatterned microplates.
- Scaffold free methods allow self-assembly of cells into 3D spheroids such as hanging drop plates, rotating bioreactors and magnetic levitation.
Shyamtanu and Orpita discuss the implications of 3D cultures in their SciWri Podcast.
What’s the history?
Who are the key players in commercializing 3D cultures?
Apart from the big names such as Thermo Fisher Scientific, Merck, VWR International, Lonza group, Corning, 3D Biotek, Kuraray, ReproCELL, BD; a huge number of start-ups are investing in developing 3D culture diagnostics including InSphero, Kiyatec, N3d Bioscience. Europe has had a head start in this market due to greater awareness amongst people about its benefits, extensive research and growing investments.
Here, I highlight a few start-ups and their strengths in this field.
InSphero: Spin-off from ETH, Zurich; they deal in microtissues and scaffold-free methods. They are aiming for applications in pharmascreening and diagnostics, and to this end, they have collaborated with PerkinElmer on assay development for drug toxicity.
— InSphero (@InSphero) April 5, 2017
N3d Bioscience: What sets them apart is the levitation method of the 3D culture. By attaching nanoparticles to the cell membrane, cells are magnetized and the spheroids are formed by applying magnets. The company based in Texas, was awarded SBIR grant from the National Science Foundation and their products are now available in the market. They will soon be moving into application of 3D cell culture to Regenerative Medicine.
300 Microns: A start-up venture of scientists from Karlsruhe institute of Technology, Germany. 300uM, happens to be the natural distance between two capillaries in an animal tissue and ‘300 Microns’ produce special polymers housing microcavities in the 300uM range. These polymers can be tailor-made to the consumer’s needs varying in geometries, diameter and shape of microcavities and permeability of the polymer.
AIM Biotech: Based in Singapore, they specialize in microfluidic chips for 3D cell culture. These chips can be utilized for co-culture of different cell types. In 2016, within 4 years of establishment, the MIT spin-off company partnered with distributors from USA, Japan, Europe and China expanding their customer-base.
Kiyatec: Focusing on cancer therapeutics, they create customised in-vivo like models for drug response profiling, with the aim to evaluate drug toxicity before proceeding with human clinical trials. Founded by Clemson university alumni, they were recently awarded two SBIR grants: one for progressing their work on 3D breast cancer model by the National Cancer Institute and another one for developing a microbioreactor mimicking live bone marrow.
— NCI SBIR (@NCIsbir) April 3, 2017
Creative Bioarray: Initially specialising in array products, now they provide a wide range of products for research comprising of various cell types, ready-to-use 3D cell cultures and protocols for 3D model development. Based in New York, they are one of the leading producers of cell lines used in research.
Organogenix: Formerly Scivax, Japan, they develop dishes for spheroid formations. Owned by the JSR corporation, they specialize in scaffold-based 3D cell culture and provide consultation as well as contract services for establishing these methods.
Pandorum Technologies: Based out of Bangalore (India), Pandorum Technologies creates 3D-printed human tissues for medical research and therapeutics. Pandorum was the first in India to design and 3D-print human liver tissues for medical research. The startup is currently working on bio-engineering implantable human cornea. Its 3D-printed human tissues are applicable in medical research for drug metabolism and disease modelling. Pandorum’s bigger vision is to make personalized on-demand human organs such as lungs, liver, kidney and pancreas.
— Think Change India (@ThinkChangeIND) March 13, 2016
Applications and Major Consumers
Drug Discovery: Traditionally, tests for a new drug go from 2D cell culture to animal models, before starting with clinical trials on humans, which in itself is a long, laborious process, sometimes spanning a decade. However, 2D cultures have a major draw-back: being mono-layers, the results of drug toxicity in these conditions can be misleading. 3D cultures are much more representative of the in-vivo environment. These cells grown in 3D media and organoids will soon be able to replace the use of animal models, providing clinically relevant tests for drugs that pass to human trials.
Regenerative medicine: The shortage of organs for transplantations has led to adoption of strategies for growing tissues and organoids in petri dishes. There have been success stories for artificial implants, but it’s a long way to go before this becomes a norm. Unsurprisingly, biotechnology and pharmaceutical Industry is the leading end user for these diagnostics. The need for advanced drugs, with minimal animal testing and search for better diagnostics is pushing pharmaceutical companies to adopt 3D cultures.
Basic Research: 3D cultures are becoming popular amongst basic research scientists; since 3D cultures maintain cell morphology and give a more realistic response to candidate small molecules. Especially, the field of cancer biology is moving rapidly and the assays are now being designed to ensure cells grow in a close-to-natural environment.
Challenges and Outlook
These cultures require huge financial investments which is a major concern for wide application in basic research, restricting its usage to certain institutes. Other caveats such as scale and practicality need to be overcome in the near future. With a wide range of applications, 3D cultures are here to stay! The value for global 3D culture market, as of 2016 is US$ 456.8Mn and is projected to reach US$ 2,734.3 Mn by 2025.
Watch out for
Microfluidics (Organs on chip) and Organoids
— Brennen Hodge (@BrennenHodge) September 30, 2017
In a Nutshell
In North America- USA and in Europe- Germany.
Fastest Growing market- Asia Pacific.
As of 2016, value for global 3D cell culture market, is US$ 456.8Mn and is projected to reach US$ 2,734.3 Mn by 2025.
And finally, for a career inspiration hear this TED talk by the Cellular Therapeutics CEO, Robert Hariri, talks about his research in using placenta-derived stem cells as novel therapy for Crohn’s disease, and to create new “organoids” for research and transplants.
In his career as neurosurgeon and trauma specialist at Cornell University, biotechnology executive, military surgeon and aviator, Dr. Hariri is most recognized for his discovery of pluripotent stem cells from placenta and as a member of the team which discovered TNF (tumor necrosis factor). Dr. Hariri was awarded the Thomas Alva Edison Award in 2007 for his discovery of placental stem cells and again in 2011 for engineering tissues and organs from stem cells.- From TedMed
References and further reading:
About the Author:
Heena is interested in scientific writing, communication and outreach. She did her PhD in Strasbourg and is currently working as a postdoctoral fellow at EMBL, Heidelberg; with experience in the field of molecular, cellular and structural biology. When she is not in the lab, she can be found promoting open access to other researchers or discussing scientific research with students, and travelling to offbeat destinations
About the Podcasters:
Orpita Dey has pursued her M.Sc in Microbiology from Bangalore University. She is currently working as a consultant copy editor for Newgen Knowledge Works. She edits STEM publications and also books on Humanities. She has worked in the past with organizations like Thomson Reuters, ANSR Source, and Education First. She is a science enthusiast and loves to learn new languages. Presently, she is learning German from Dallas Goethe Institute.
Shyamtanu Datta pursued his Ph.D. in Biomedicine (Molecular and Cellular Ophthalmology) from Universität Klinikum Regensburg (Regensburg, Germany). He is currently working as a postdoc at department of Ophthalmology in UT Southwestern Medical Center (Dallas, Texas). He is passionate in learning about business of science which translates from bench to bedside. With over 8 years of experience in research and education, he also wants to contribute to educational innovation for the next generation by making science education more personalized, interesting and fun for the next generation. He loves to travel and learn new technologies.
Cover Image: Vinita Bharat
Infographics and Blog design: Abhinav Dey
This work by ClubSciWri is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.