Cell-expansion technology is a critical component in various fields of biotechnology and regenerative medicine, focusing on the growth and proliferation of cells to meet the demands for clinical, research, and industrial applications. Cell-expansion technology is a cornerstone of modern biotechnology, enabling advances in medical treatments, drug development, and sustainable industrial processes. Ongoing innovations and improvements in this field hold great promise for addressing some of the most pressing challenges in health care, environmental sustainability, and cellular agriculture. In this interview with TechBullion, Lior Raviv, CTO at Pluri, shares how the company is pushing boundaries within the biotechnology industry.
Please tell us more about yourself and your journey before Pluri?
My name is Lior Raviv, and I’m the Chief Technology Officer for Pluri. I’ve been with the company for the last 13 years, starting in the development department with a focus mainly on developing the cell expansion technology and process. Over the years, I was given more and more responsibilities and, today, I oversee development, clinical manufacturing, and operations. What excites me most is how our team conceptualizes ideas and then moves them all the way through, starting with research and development through full deployment of the products to different customers.
What is Pluri? What are the unique solutions that you provide? And could you give us more insight into your role as the CTO at Pluri?
Twenty years ago, Pluri started as a clinical biopharmaceutical company focused on developing allogeneic cell therapy products, using cells extracted from a single placenta and then expanding those cells into huge quantities intended for many patients. Over time, we realized that our true value proposition lay with our know-how in cell manufacturing industrialization and proprietary 3D bioreactor technology, which lends itself to scaling up a wide range of cells (e.g. allogeneic cells, including IPSCs, MSCs, immunological cells, exosomes and viral vector-modified cells, etc.). Therefore, as we continued to develop clinical therapeutics for human use, we began on a parallel path to further develop our technology to address other needs in our global community. All life begins with cells, and our technology has applications to address problems related to a growing and aging population, climate change, environmental concerns, ethical production of food, food scarcity and so much more.
As the CTO, my team and I looked at the common bottlenecks in manufacturing cells to see how we could enhance the process. As Pluri continued to grow, we kept developing new technologies and boosting the scale of our bioreactors. Eventually, we created the PluriMatrix, and we learned that in addition to growing human cells for pharmacological purposes, we can grow other cell types (animal and plant) that help other industries. And we can grow these cells at mass scale.
What types of cells can be grown using Pluri’s technology, what is the 3D cell-expansion technology about, and how does it differ from traditional cell culture methods?
When we look around us, we see humans, animals and plants, all of which are 3D structures, but most of the early cell-expansion technologies focus on suspension. If you take simple cells like yeast, which are used to brew beer, you can grow them into mass scales in your own tanks using suspension technology. However, when you look at the more complex cells in 3D structures and try to scale them up, you need a lot of force to mix the suspension and create the right conditions in which to grow those cells. Complex cells are sensitive to those forces, so they don’t grow as well when you try to scale them up using suspension technologies.
Hence, this is the biggest challenge in cell manufacturing because while you can get good results in a smaller bioreactor using the suspension method, you cannot scale up to hundreds or thousands of liters; The cells do not grow and expand very well. Pluri solved this problem and created a new way to grow cells by using scaffold technologies inside our bioreactors. Human cells attach to the scaffolds and start creating tissue inside them. We call our system “3D” specifically because we use a packed-bed bioreactor instead of a suspension base. It’s a completely new way of growing cells because we provide the cells the conditions they are used to growing in, which preserves their biology.
Notably, we started with human cells, but now know that we can use the system for other types of non-human cells by adjusting various parameters inside the bioreactor. Specifically, our technology is being used to expand animal cells for cultivated meat and plant cells (those of the coffee plant) to develop cell-based coffee.
What advancements have been made in science and technology through the use of 3D cell-expansion technology, could you give us more insights into this 3D cell-expansion technology market?
Through the 20 years of working inside and expanding cells, we learned many things. Understanding cells and learning how to industrialize biology are crucial, and we’ve created a lot of technologies to address these areas. If you’re going to grow cells, it’s not enough just to have a large bioreactor. You also need to understand what those specific cells need to grow so that you can mimic their natural environment inside the bioreactor.
I think the PluriMatrix is one of the most crucial advances that we’ve made. The PluriMatrix is a new type of bioreactor we created based on all the existing data and technologies that we had. As I mentioned, the challenge was creating mass-scale bioreactors while preserving the 3D cell culture, so we created what we call a flow chamber. It’s a column filled with scaffolds, and it basically has a main pipe that goes into and out of it, kind of like an artery and a vein, and it’s connected to a large bioreactor that holds hundreds of thousands of liters. Everything that must be controlled on the media is in the bioreactor, including oxygen, nutrients, and everything else, and the bioreactor mixes a lot of forces, but the cells are protected because they’re not actually in the bioreactor. They are connected through these kinds of arteries and veins to the flow chambers and then the cells only feel the forces that we want them to feel by controlling the conditions.
We learned that when we work like this, we can actually connect almost unlimited numbers of chambers to one system, just like our body or animal bodies are made with many organs connected to the system in 3D. This technology is unlike any other, which is why when we demonstrated it to our now partner Tnuva Group for the manufacture of cultivated meat, which is how they realized they could manufacture tons of cultivated meat products. So the advances we’ve made in industrializing and controlling the process and the final system actually open the door to creating new industries or solutions.
As the global leader in 3D cell-expansion technology, could you give us a walkthrough of the Pluri ecosystem, the process for manufacturing future products and solutions and how these ideas come to fruition?
This will sound odd, but the way we work is actually by trying to kill new ideas. We start with a brainstorming session, and then we research and try to look for data and reasons an idea won’t work, and that’s how we learn. For example, to create new products in the cultivated-meat industry, we need to isolate cells from the desired species and then grow the cells, so we check the literature for data suggesting it won’t work. If we don’t find any, then we move forward and try to do it. It’s kind of an evolutionary process. We start with the hardest parts first to see if they will work because if they don’t, there’s no reason to advance the idea any further.
The potential applications for this technology go beyond just the pharmaceutical industry, it also benefits the food tech and agri-tech industries. Could you highlight some of these industries and what impacts Pluri is making?
As I mentioned, when our research proved that we can work with different types of cells, it led to a new idea of growing animal cells to produce meat without harming any actual, fully grown animals. Instead, we biopsy an animal for its cells and then expand them to create the desired product.
At first, we didn’t imagine that our work with animal cells would generate interest from the agritech sector. However, we’re proud that our research, development, and technology has opened a new field, not only in the industrial scaling of cultivated meat, but also in agriculture. Our work with plant cells led to the development of cell-based coffee, which we can produce at scale with a dramatically reduced infrastructure footprint and remarkably lower environmental impact. There really is unlimited potential to create even when you start from something as small as a single cell.
Pluri’s technology has been successfully used to accelerate the development of pharmaceutical products. How does Pluri support research and development in the pharmaceutical industry and how are these projects funded?
Pluri is continuing clinical biopharmaceutical research, developing cell-based therapeutics that will address muscle injuries, inflammatory diseases, and acute radiation syndrome (in partnership with the U.S. National Institutes of Health), to name a few. Notably, we recently launched a placental allogeneic MAIT cell platform for immunotherapy treatment for solid tumors – a significant medical need which currently lacks effective treatments – using a newly patented method for expansion of immune cells using our proprietary technology.
But in addition to advancing our new and existing products, we recently formed a contract and development manufacturing organization, or CDMO. From development of scalable manufacturing processes to quality control to global logistics, PluriCDMO offers flexible, comprehensive support for cell therapy manufacturing needs. When we partner with strategic collaborators that seek support for their product or process, we leverage all of our expertise to create the best solutions for those partners, helping them to advance through the technical and clinical stages of their products.
Our CDMO team has successfully led cell culture manufacturing for 10 clinical trials globally, ensuring compliance with all regulatory standards. From cell expansion to freeze/thaw, to shipping, storage and stability, our know-how is as important as our technology when it comes to working with our partners.
As the CTO, could you share your insights on how Pluri’s innovative technology is changing the game in cell expansion and why Pluri’s 3D cell-expansion technology is more efficient and cost-effective than traditional methods?
As I mentioned, 3D cell growth is unique, and we’ve created a lot of intellectual property around that to grow and expand different types of cells. Not only does our technology grow cells reliably, sustainably and at large scale in a more natural environment, but we also require a smaller physical manufacturing footprint, meaning that cost is reduced because you need smaller infrastructure. Additionally, we need less capital to set up this system, which also creates a lot more cells than previously-existing technologies.
We would like to hear more about some real-world examples of how Pluri’s technology has been successfully applied to different industries, the challenges faced and success stories so far?
Pluri is a technology company focused on cell expansion. We are primary investors in Ever After Foods, which is a subsidiary using our technology to develop a platform for food producers to grow cultivated meat at scale. We are also working on another subsidiary that will focus on cell-based coffee, plus we recently announced a partnership with Wilk that will explore the development of an adult medical food developed from breast milk cells.
We hope our CDMO will soon announce additional partners, and, in addition to all of this, we also continue to develop our technology and are bringing several human drug candidates through the clinical-trial process.
What are Pluri’s future plans to continue evolving and expanding its technologies to drive further innovation, do you have any available opportunities for investors or partnerships to support these life-changing projects?
As mentioned earlier, we are working across sectors – from regenerative medicine to agritech – to bring cell-based products to life (pun intended). Our best-in-class technology is attractive to partners seeking to advance their products, which is why we regularly collaborate with partners and started a CDMO vertical. We believe that our vision of the potential of cells is attractive to investors.
