What if the solution to cell therapy’s biggest cold-chain challenge comes from the biology of Arctic fish?

Cryopreservation is the linchpin of cell and gene therapy logistics—and for years, dimethyl sulfoxide (DMSO) has been the industry’s reluctant standard. DMSO keeps cells alive in the freezer, but at a cost: regulatory headaches, damaged cells, patient side effects, and complicated workflows. So what if an antifreeze-inspired innovation could finally retire DMSO for good?

This conversation features Steve Oh, a leader in advanced bioprocessing, whose career has placed him at the intersection of stem cell biology, process engineering, and clinical translation. Steve Oh joins David Brühlmann to share how a next-generation cryopreservation solution drawing from nature’s antifreeze proteins—lets cells survive, thrive, and simplify manufacturing from the bench to the clinic.

Key Topics Discussed

• XT-Thrive® demonstrates improved cell viability, proliferation, and functionality compared to DMSO across T cells and MSCs.
• The solution maintains consistent performance across different cell types and culture conditions, including serum-free systems.
• Its mechanism reduces ice crystal damage, leading to better post-thaw recovery and cell yield.
• XT-Thrive® simplifies workflows by eliminating wash steps and extending processing windows after thawing.
• Enhanced temperature flexibility and reduced contamination risk improve logistics for both autologous and allogeneic therapies.
• The solution integrates easily into existing GMP workflows with plug-and-play adoption and global scalability.
• Broader cell therapy challenges remain, including differentiation time, product consistency, and cost efficiency.
• XT-Thrive® offers a non-toxic, user-friendly alternative that could reshape cryopreservation and cell therapy practices.

Episode Highlights

• Biological insights from Arctic fish and their translation into synthetic peptide chemistry for cell preservation [00:23]
• The effect of ice crystal formation on cellular damage, and how XT-Thrive® minimizes this compared to DMSO [05:32]
• Simplified logistics: reduced risk of contamination, elimination of post-thaw wash steps, and implications for therapy delivery to remote locations [07:23]
• Applicability beyond single cells—preserving organoids and potential implications for tissue engineering [09:50]
• The ease of transitioning from DMSO to the new solution in established lab protocols [10:49]
• Broader industry challenges: maintaining purity, process optimization, and reducing cost of goods in cell therapy manufacturing [12:03]
• Promising innovations in rapid cell type differentiation and barriers to scaling transformative biotech [12:50]
• The importance of supporting innovative therapies beyond short-term ROI [14:17]

In Their Words

It is really a simple plug-and-play solution. It's been made to GMP grade. It has a Drug Master File. So it's simply just getting a bottle and then using it at the same concentration as you would currently use with DMSO at 5% or 10%. So most cells would just transition from DMSO to the solution without any problem.

DMSO in Cell Therapy: Why Viability Scores Hide the Real Toxicity - Part 2

David Brühlmann [00:00:23]:
Arctic fish survive in waters that would freeze most life solid. That biological insight, translated into synthetic peptide chemistry, may be exactly what cell therapy manufacturing has been waiting for. In part 1, Steve Oh walked us through the DMSO problem in depth: the toxicity, the cellular damage, the regulatory pressure. Now we get to solutions: from cryopreservation performance data to manufacturing logistics to what a transition actually requires. This is where it gets practical.

Can you give us some examples, Steve, of how this innovative approach helps cells survive better and maintain their viability and function?

Steve Oh [00:02:23]:
We have a presentation on various cell types, both T cells and MSCs. So we have an example where fresh pan-T cells isolated from donor apheresis were stored at 10 million cells per mL, and then they were frozen down for 40 days with the XT5 solution. And post-recovery, they were able to proliferate as well as the fresh product.

Another example was when we preserved T cells from two CDMO partners. The XT-Thrive® frozen product had almost equivalent—about 80%—secretion of IL-2, similar to fresh cells, whereas the DMSO-containing product was around 60%. And in terms of the immunophenotype, they expressed CD4/CD8 markers.

In terms of cytotoxic function, four DMSO-containing competitor products were tested against the XT-TRI solution at effector-to-target ratios of 1:1 and 0.3:1. So XT-Thrive® had the best performance in terms of cell-killing function over the other three DMSO-containing products. In fact, one product had no killing efficacy at all at the lowest effector-to-target ratio.

A third example is when CD4 and CD8 T cells were frozen for 7 days and then thawed, and nucleofection of the CAR-T gene was performed. The efficacy was about 80% for XT-Thrive® versus 60% for the CryoStor CS10 cryopreservation solution. These are the T-cell examples, where we’ve seen much better performance than CS10.

In terms of MSCs, we looked at holding the cells in solution for 24 hours prior to freezing. We found that the viability of the cells held in XT-Thrive® remained at about 90%, but DMSO dropped progressively—within 4 hours to 85%, and then overnight down to 60%.

Then when we froze and thawed them, recovery of viability was about 90% for XT-Thrive® and about 85% for CryoStor CS10, and it continued to drop to about 60% over 8 hours, whereas XT-Thrive® was maintained around 90% in MSC cultures.

All these experiments were done under both serum-containing and serum-free conditions. Many products are moving toward defined serum-free conditions, and cells tend to be more sensitive without the serum background. So we've seen this performance to be consistent irrespective of serum-free or serum-containing conditions.

And finally, when we put these cells back into culture on microcarriers—which is a scalable method for cell production—we saw immediate recovery and growth of the cultures post-thaw with XT-Thrive®. But with DMSO, there was a 4-day lag followed by only marginal growth. So overall, we observed about a 2.5-fold increase in cell yield post-thaw.

David Brühlmann [00:05:20]:
To what extent, Steve, were these stark differences between XT-Thrive® and DMSO due to ice crystal formation and differences, I'd say, in mechanism?

Steve Oh [00:05:32]:
I think that is the key benefit of this approach. We have seen in microscopic studies that ice crystals are relatively large in water, and with both antifreeze proteins and the XT-Thrive® product, the crystal size is reduced to about 10–50% of that seen in water. So most of the damage actually occurs during thawing, when these crystals can cause mechanical damage to the cell membrane if thawing is not rapid enough.

David Brühlmann [00:06:01]:
Let's shift gears here, Steve. So we have seen the stark differences between DMSO and this novel solution. We have also talked about the main challenges linked to DMSO. Now, another question we need to tackle is: we have a new product that seems to work well, but how does this affect established workflows—washing, freezing and thawing, temperature? Can you give us a picture there? What changes for the person doing the work in the lab?

Steve Oh [00:06:33]:
So one of the first things we did was to run a hold-time experiment over 24 hours. We learned in the early days that once you put cells in DMSO, you have to process them quickly—within 4 hours, but ideally between 30 minutes to 2 hours.

That’s fine when you're using small vials of cells that you can aliquot at 1 mL each. But once you're processing, say, 100 mL bags—or even a 1 L batch that you then aliquot into 100 mL bags—that workflow becomes very rushed.

So that's why we did the real-time hold experiment over 24 hours, to ensure that cells could be processed over a full day and to assess whether viability would be affected. And sure enough, we found that viability was maintained over the 24 hours, which makes processing much more convenient.

On the backend, there were also tests where the solution was injected into animals at 100× the concentration used for cryopreservation, and there was no toxicity observed. So there isn’t the same requirement to wash away the DMSO-containing solution—you could inject it as is post-thaw. It behaves almost like water—not exactly, but it is essentially non-toxic.

So you can inject it into the patient without that extra wash step. Again, this reduces the risk of contamination due to manual washing and centrifugation steps, and significantly simplifies the workflow from both a manufacturing and point-of-care delivery perspective.

David Brühlmann [00:08:01]:
How does this simplified workflow without an additional wash step after thawing affect—or facilitate—the distribution of these therapies to remote locations? Because that's one of the challenges we are still facing in cell and gene therapy: how do we bring these therapies from the manufacturing site—whether it's a hospital or a company—to the patient?

Steve Oh [00:08:27]:
So we have tested the solutions at 4°C, −80°C, and −196°C. Across all these temperatures, cell viability and performance are as good as or better than with DMSO. So in autologous therapy, you can hold the cells at 4°C for as long as needed for transportation. In manufacturing, you can create master cell banks and working cell banks at −80°C to −196°C. And for allogeneic therapy, you can handle much larger volumes, enable long-term preservation over years, and then thaw the cells for localized treatment.

One of the benefits of being able to operate at 4°C is that, as I’ll mention later, you can transport certain cell types—like organoids or even organs—for 3 to 5 days at cold temperatures without freezing. So they never form ice crystals. You can transport them across the country, and the organs are still functional after warming. So again, it highlights the versatility of the solution compared to DMSO.

David Brühlmann [00:09:39]:
So am I hearing correctly that this product cannot only be used for single cells, but for organoids and potentially even in tissue engineering or some other areas?

Steve Oh [00:09:50]:
Yeah, that's right. We don't have published data yet, but there is accumulated evidence that heart islets are functioning in XT-Thrive®, and the XT -Novo data for larger human organs will be coming up. So at ISCT, in May 2026 in Dublin, we should have more data on these different cell types, including organoids.

And organoids have their own challenges because they are fairly large structures—up to 5–10 millimeters in size—and they need to be kept cold or produced fresh because there’s traditionally no good way to freeze them down or hold them at cold temperatures. And we think we have some good data to show for that.

David Brühlmann [00:10:31]:
Let's assume that my team and I have developed a T-cell process using DMSO, and now I'm listening to this podcast and I learn about this much better product to freeze and thaw cells. How easily can I switch over to this new product?

Steve Oh [00:10:49]:
I think it is really a simple plug-and-play solution. It's been made to GMP grade. It has Drug Master Files. So it's simply just getting a bottle and then using it at the same concentration as you would currently use with DMSO at 5% or 10%. So most cells would just transition from DMSO to the solution without any problem.

In terms of the manufacturing facilities, there are sites in San Francisco and Vienna, and clients are welcome to visit them to audit the manufacturing process. We are also talking to some major distributors in the US and Japan to extend the global reach.

David Brühlmann [00:11:28]:
Let's zoom out and look at the broader cell and gene therapy picture. There's a lot of innovation happening. Beyond DMSO, what are some impactful areas you're seeing or some promising areas that you think are worthwhile highlighting?

Steve Oh [00:11:48]:
Related to cryopreservation or beyond cryopreservation?

David Brühlmann [00:11:51]:
In general, beyond cryopreservation.

Steve Oh [00:11:54]:
I think the biggest challenge with stem cell–based therapies is the long differentiation time from the starting material to the final product. That's one challenge.

The second is maintaining the consistency and purity of the target population, whether it be neural stem cells for Parkinson’s disease trials or cardiomyocytes for heart disease. So this remains an ongoing challenge.

The third challenge is achieving this at a low cost of goods. Process optimization is key here, just as in biologics manufacturing, because many protocols rely on numerous combinations of growth factors and small molecules to generate the final cell type over many weeks.

So I think the cost of goods, due to the complexity of the process, will determine whether we achieve widespread adoption of these cell therapies.

David Brühlmann [00:12:43]:
What technology innovations have you seen that you think could solve one of these challenges?

Steve Oh [00:12:50]:
I have seen some data from a company called Accelerated Biosciences, using a source of cells called trophoblast stem cells. They had data showing that with a one-day induction, they could produce a cell type that secretes dopamine. And when injected into mouse models of Parkinson’s disease, they were able to recover function.

But that company has been facing challenges raising funds to move into a Phase 1 clinical trial. So if a transformative technology like that can generate a functional cell type—similar to a dopaminergic neuron—in just one day, that would be fantastic in terms of process efficiency, manufacturing, and cost of goods. But it has not yet reached Phase 1 clinical trials.

David Brühlmann [00:13:34]:
Such an innovation would move the needle forward, but it's a pity to see disruptive technology stall because of a lack of funding. I mean, it looks very promising. Even later, perhaps you might run into some technical issues—who knows—but it is at least worthwhile pursuing the development and seeing whether it will work in a commercial setting.

Steve Oh [00:13:58]:
If you had the opportunity, it might be good to get a venture capitalist or someone from the investment side who can talk about what needs to be addressed to unlock funding.

David Brühlmann [00:14:08]:
Yeah, absolutely. And if one of the venture capitalists is listening, this is an opportunity. We are in the money game, yes, but I think we should also have a broader perspective. That's at least my personal view of the industry.

We should pursue technologies that don’t have an immediate return on investment because, at the end of the day, we’re in it to treat patients. So I think this is something that, if I may say, our industry could further develop—the social dimension of innovation—not only the immediate ROI.

Well, this has been great, Steve. Before we wrap up, what burning question haven't I asked that you are eager to share with our biotech community?

Steve Oh [00:14:52]:
I think in terms of disruptive technology, XT-Thrive®, this single cryopreservation solution, will contribute significantly to cell-based therapies because it has zero toxicity. It preserves cells and tissues in a much better state than traditional DMSO across many different cell types. Recovery of cells post-storage is much higher—more viable, functional, and healthier.

It doesn't need a wash step, and it doesn't cause irritation or edema at the site of injection, which makes it easier to administer to patients. So I think this will be one of the key solutions in cell therapies, impacting both current T-cell–based therapies and future stem cell therapies. Thank you for the opportunity to speak about this topic.

David Brühlmann [00:15:38]:
Absolutely. It's a pleasure. And if there is only one thing you want our listeners to walk away with, what would it be?

Steve Oh [00:15:46]:
If you're looking for a cryopreservation solution, just reach out.

David Brühlmann [00:15:59]:
Okay. So this leads me to the final question, Steve. Where can people get ahold of you and this product?

Steve Oh [00:16:05]:
So I'm on LinkedIn, and my email—if you can share it—is skwoh.so@gmail.com.

David Brühlmann [00:16:15]:
There you have it, Smart Biotech Scientists. You will find the link in the show notes. Reach out to Steve and his team. And thank you, Steve, so much for being on the show today and sharing both the challenges and solutions in cryopreservation.

Steve Oh [00:16:30]:
Thank you so much. Thanks, David.

David Brühlmann [00:16:34]:
From Arctic antifreeze proteins to clinical-grade cryopreservation, Steve Oh has shown us that the DMSO era may finally have a credible successor. The performance data is compelling, and the manufacturing implications are significant. If you're navigating these challenges in your own program, I hope this conversation gave you a clearer path forward.

And if it did, please take a moment to leave a review on Apple Podcasts or your favorite platform and share it with a colleague. For additional bioprocessing tips, visit www.smartbiotechscientist.com. Stay tuned for more inspiring biotech insights in our next episode. Until then, let's continue to smarten up biotech.

Disclaimer: This transcript was generated with the assistance of artificial intelligence. While efforts have been made to ensure accuracy, it may contain errors, omissions, or misinterpretations. The text has been lightly edited and optimized for readability and flow. Please do not rely on it as a verbatim record.

Next Step

Book a free consultation to help you get started on any questions you may have about bioprocess development: https://bruehlmann-consulting.com/call

About Steve Oh

Steve Oh is a seasoned biotech scientist and advisor with a career defined by innovation and resilience. After more than two decades at A*STAR’s Bioprocessing Technology Institute, where he developed cutting-edge stem cell and bioprocessing technologies, he transitioned into entrepreneurship and advisory roles across the global biotech ecosystem. 

Despite early challenges in launching spin-off ventures, he leveraged those experiences to guide companies in areas such as viral vector manufacturing, cultured meat, and advanced cell therapies. He continues to shape the future of biotechnology through research collaborations, advisory work, and mentorship.

Connect with Steve Oh on LinkedIn.

Further Listening

If you’re interested in this topic, check out these episodes, where we explore how Minnesota’s frozen forests inspired a new wave of biotech innovation, transforming how life-saving cells are frozen, stored, and shipped.

Episodes 161 - 162: How to Achieve 85%+ Cell Recovery Without DMSO's Toxic Side Effects with Jeffrey Allen

This is Steve’s second appearance on the podcast. You can also catch his earlier conversation with David, where they explored the challenges and opportunities of cell and gene therapy.

Episodes 11 - 12: From Lab to Patient: Steve Oh’s Guide to Mastering Cell Therapy Process Development.

He is also a biotech technology innovation coach, technology transfer leader, and host of the Smart Biotech Scientist podcast—the go-to podcast for biotech scientists who want to master biopharma CMC development and biomanufacturing.  

Hear It From The Horse’s Mouth

Want to listen to the full interview? Go to Smart Biotech Scientist Podcast. 

Want to hear more? Do visit the podcast page and check out other episodes. 
Do you wish to simplify your biologics drug development project? Contact Us