SBI’s conference on the Latest Advances 2021: Oxygen and pH Sensing in Cell Culture brought together renowned subject matter experts for a full day of presentations, panel sessions, and dialog about the future of sensing, cell culture, and drug and device development.
The conference kicked off with a fascinating keynote by Dr. Doris Taylor, the CEO of RegenMedix Consulting and a pioneer in cardiovascular regenerative medicine. Her presentation, “Organ Engineering in 2020 and Beyond: Overcoming Technical Hurdles,” provided a fascinating look at the trajectory of tissue engineering from its origins in the bone marrow transplants of the 1960s to the advances in 3D bioprinting and the use of induced pluripotent stem cells (iPSCs) of today.
“We have this tremendous opportunity to address the great unmet need for organs. The donor need list adds a person every nine minutes. Recently, there were 109,000 people on the transplant list, and only about 40,000 transplants were done last year. 847,000 people die of heart disease every year and 2,600 people need a heart annually and only about 2,300 hearts were available,” stated Taylor.
Regenerative medicine has come a long way since the 1960s. Gene therapy arose in the 1990s, stem cell therapies emerged in the 2000s, and by 2010, iPSCs technologies and 3D bioprinting changed the game for tissue and organ engineering. Taylor noted that the field has so much promise, but daunting challenges remain when it comes to creating organs at scale for human transplantation.
“The challenge is moving from small scale to larger scale. Bioprinters can build a mini-heart, but they are too small and don’t have blood vessels. 3D printing is just not there yet to build vascular networks. We have high hopes, but we’re not quite there yet. The ‘holy grail’ is creating vasculature,” stated Taylor.
Taylor went on to say that decellularization is currently a better option for organ engineering experiments until 3D bioprinting advances. The decellularization process removes cells and genetic material from a human heart, for example, while ideally leaving the biochemical and biomechanical structures in place. The structure of the heart remains intact and is then, in theory, repopulated with a transplant recipient’s own cells, thus engineering a replacement heart that is not only functional but also personalized to the patient.
Decellularization has the potential to solve the scaling challenges faced by 3D bioprinters that cannot create vasculature or an organ at the scale required to function in a human body. However, decellularization faces its own set of issues regarding scalability, according to Taylor.
“Decellularization is very expensive, and it takes a lot of time. There is no supply chain; it is non-existent and needs to be built from scratch. The scaffolds, cells, media, bioreactors, and assays need to be built from scratch,” stated Taylor.
“What we need to build a complex organ is a closed system from scaffold all the way to a functional heart. There are many technical challenges, including the risk of contamination, but what’s really needed is the ability to sense biomarkers, glucose, metabolism, and hypoxia at the very beginning of the process in a non-invasive way,” she added.
To create a functioning human heart requires the creation of billions and billions of healthy cells that will function well within the human body. Non-invasive sensing during the production of these cells and automation that will keep the system closed are both critical to making the process more efficient, more scalable, and ultimately less labor-intensive and expensive, according to Taylor.
In an ideal scenario, the required materials would be input into one end of a fully automated closed tissue engineering system, non-invasive sensing would generate essential data and provide real-time monitoring at every stage of the process, and a fully functional, ready to transplant human heart would come out the other end with no invasive human manipulation.
“The scaffold design for engineering human hearts is mostly solved. Recellularization has both technical and financial hurdles. A small heart requires six billion myocytes, 1.5 billion endothelial cells, and 160 liters of media to survive,” shared Taylor.
“That’s $60 to $80K per small heart. We need sensing to reduce this cost and make this process real,” she added. “We also need intelligent bioreactors to achieve a closed system to recreate the extracellular environment of human development,” she added.
“Historically, we’ve not had a good way to measure or evaluate. We had to stick electrodes and catheters into organ structures. We’ve been missing the closed system, durable monitoring of pH, O2, and glucose, and dynamic, more sensitive inputs. We need more non-destructive analysis,” stated Taylor.
“We need to work with industry to develop these tools to achieve clinically relevant endpoints. We need to be able to monitor data in real-time at the cellular level. Right now we eyeball. How primitive is that? We need real-time measurement at scale, new imaging tools, and we need to know if cells are healthy, alive, and aligned to make faster go, no-go decisions,” she implored.
Taylor believes that creating functional bioartificial hearts and other organs at scale, for less cost, and in less time is possible if the industry can develop more durable, sterilizable, modular, and reusable tools for tissue engineering.
“If we can get there, we can create a bioartificial human heart that begins to beat right in seven weeks with 95% cellularity of a real human heart,” shared Taylor.
This would be revolutionary and science fiction made a reality. Bioartificial hearts and other engineered organs could save thousands and perhaps hundreds of thousands of lives every year, delivering a new and better lease of life for patients across the globe.
SBI was thrilled to host Dr. Taylor at its virtual conference and is excited that its optical sensors will play an important role in making organ and tissue engineering a viable option for patients in the near future.