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RWTH startup impresses Frank Thelen with stem cell incubator

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RWTH startup impresses Frank Thelen with stem cell incubator

Although Frank Thelen (l.) is more enthusiastic about software, this time his money is going to a hardware startup. The Biothrust founders are happy (from left to right): Patrick Bongartz, Konstantin Kurz and Moritz Meyer. Biothrust

Patrick Bongartz felt that his stem cell proliferation technology should be more than just the result of his doctoral thesis. When he met mechanical engineering student Moritz Meyer at RWTH Aachen University during his doctorate in chemical engineering in 2016, and they developed the process together and applied for a patent, it was clear: a business could emerge from this. “Other institutes and companies had already expressed interest. So we thought about whether we could get it out of the lab so that others could benefit from it,” says the founder. The team was formed with WHU member Konstantin Kurz, who previously worked as a consultant at Oliver Wyman and met both of them in 2020 through the university’s co-founder matching. In 2022 they founded the biotech startup Biothrust.

At first glance, the container is reminiscent of a swimming pool filter or an unusual salad spinner. Over 60 white rods made of a special plastic, known in technical jargon as “hollow fibers”, rotate in the tub. Bioengineer Bongartz compares them to macaroni noodles, which pass air currents, more precisely oxygen and CO2, through their interior for the metabolism of the cells. The outside of the plastic tube is surrounded by amniotic fluid, like that in which human embryos swim. The device is called a “binomial bioreactor”. Thousands of stem cells mature here under natural conditions and could one day help many patients with difficult-to-cure diseases such as Parkinson’s, Alzheimer’s, myocarditis, various types of cancer, diabetes I and knee arthrosis. Stem cell therapies ensure that lost tissue in the body is replaced or repaired. So far, such treatment has been one thing above all: complex and expensive. The founders want to change that by producing stem cells faster and in larger quantities.

Fewer stem cells are destroyed

The special feature: no water from the outside gets through the grid-like membrane of their incubator, only dissolved gas. Molecule by molecule, explains Bongartz. This means that no gas bubbles form in the amniotic fluid solution. These are precisely the main problem in previous bioreactor processes. In order to supply the cells in the vessels, some of which contain two liters, with oxygen, gas has previously been bubbled in. However, the pressure this creates has a negative effect on the fragile stem cells. “If the gas bubbles rise at normal speed, they have enough force to destroy the sensitive cells in the area,” says Bongartz. This effect no longer applies when using Biothrust. In addition, the hollow fibers, which move slowly through the liquid like sails, ensure that nutrients are distributed evenly and cell waste products are transported away.

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In this way, the Aachen-based company also wants to be one step ahead of the “tub stack” model that Bayer uses. There, hundreds of Petri dishes are stacked on top of each other to form a mountain in order to scale stem cell production. There is no gas bubble problem with the stacks because the metabolism can simply take place over the surface of the Petri dishes as they are filled with only a small amount of liquid and a lot of air can escape. However, the same nutrient conditions do not exist everywhere, depending on whether a stem cell dish is at the top or bottom of the tower. “It works as well as playing tennis with a frying pan,” says Bongartz.

Frank Thelen invests even though startups are “unsexy”.

Co-founder Kurz emphasizes that the process is primarily about increasing the density of stem cells per milliliter. “With our device, the stem cells will not grow faster, but they will have a higher cell density in the same time because less is destroyed.” With insect cells, for example, the startup was able to show that they can produce twice as many stem cells within 48 hours as with an established system. “We assume that there is a much greater potential of at least a fourfold increase in human cells,” says Kurz. The studies continued until the summer. Based on this, the founders expect that stem cells from their bioreactor will not only be higher in quantity but also of better quality because they are exposed to less stress. This in turn could also have an influence on how well foreign stem cells are accepted by a recipient. Between 300 and 500 million stem cells are required per infusion.

Despite the medical importance of their device, the incubator developed by Biothrust does not necessarily represent the classic VC case. “A hardware that makes it possible to grow stem cells faster. That sounds extremely unsexy at first,” says investor Frank Thelen. Nevertheless, he decided to invest a low seven-figure amount in the biotech startup from Aachen through his investment company Freigeist – his first transaction in a year and a half. The reason: “We believe that you can build something good out of it and saw that the team had no other financing options, so we said: Come on, let’s do it.” Thelen further explains: “At the end of the day, it works always about scaling something so that everyone benefits from it. Stem cell therapy as it exists today is simply not affordable. But if the startup is successful, it will become accessible to everyone.”

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Stem cell therapy can cost more than 100,000 euros

In general, the costs for stem cell therapy can vary greatly. This depends, among other things, on whether the patient’s own stem cells are removed, modified and reinserted (autologous) or whether stem cells from a donor (allogeneic) are used for treatment. The latter can help hundreds of patients at once. In addition, the amount of work and high-priced organic growth materials, including hormones and artificial amniotic fluid, also factor into the costs. According to the medicine portal Knowledge show According to immunologist Volker Henn, therapies can cost between 2,000 and more than 100,000 euros if treatments have to be repeated several times. According to Bongartz, costs of up to a million dollars are not uncommon. In addition, health insurance companies only cover fees if the effectiveness of a therapy is proven and approved in the EU. As soon as there is no sufficient scientific basis, things become difficult.

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According to that Stem cell network NRW, an association that includes 24 universities, university hospitals and research institutions with a focus on stem cell research, most therapies, for example for the treatment of diabetes or Parkinson’s, are still in pre-clinical research. So far, the transplantation of bone marrow and blood stem cells, skin stem cells and corneal stem cells in the eye has been approved. In 2022, that’s what mattered Central bone marrow donor register in Germany (ZKRD) made around 6,835 stem cell donations in this country.

Startup bred miniature beating hearts

As far as Biothrust’s technology is concerned, the founders say the system is suitable for all types of stem cells. This is also necessary: ​​Because their customers, be they university hospitals, spin-offs, research institutes or the pharmaceutical industry, work with different forms depending on the disease they want to combat. In biology, a general distinction is made between embryonic stem cells, which can develop into any cell type in the human body under controlled conditions, and adult stem cells. The latter are specialized for a cell type in the human body. A special form of this is so-called induced pluripotent stem cells (iPS). They were originally adult stem cells, but can be “reprogrammed” to the embryonic form through a procedure – this opens up many possibilities for therapies.

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Biothrust has already carried out tests with iPS. “With these cells we were able to grow mini organs, i.e. small mini hearts and mini lungs that are the size of a pinhead,” says Bongartz. “You then see thousands of small balls in the reactor that start to beat. That’s really fancy!” The small organs can be used, for example, for clinical studies in which heart diseases are researched. The founders have also worked with connective tissue stem cells found in the bone marrow, known as MSCs for short.

In addition to medicine, stem cell research is used in other areas – for example in the food segment. The Aachen startup therefore sees itself in a position to also get involved in the clean meat issue. The trend is concerned with laboratory-produced meat, which is grown from animal muscle stem cells from chicken, beef or pig and could potentially one day establish itself as a climate-neutral alternative to raising and slaughtering farm animals. Another area that is of particular interest to Big Pharma is the production of biological drugs (biologics), which are obtained from modified cells of animals and plants. These include drugs to prevent blood clotting or insulin that is injected.

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By the end of 2024: Biothrust wants to bring the product to market maturity

Before their bioreactor can be used in industry, the founders first have to enter the market. As of now, their “artificial lung for bioreactors” can grow stem cells in containers that hold between 250 milliliters and two liters. The process needs to be scaled up slowly, explains Kurz. The plan is to have a market-ready product by the end of 2024. Nevertheless, the Aachen-based company wants to accept orders soon to pre-produce their device. It is not yet possible to say exactly how much the Biothrust device will cost. The controller, a mini PC with a screen that is needed to operate the bioreactor, could cost between 50,000 and 80,000 euros. In addition, there are the plastic containers of the bioreactor, which can cost between 2,000 and 3,000 euros for a two-liter volume and are only intended for one-time use.

Although the medical market is highly regulated, some obligations that some medical products have to fulfill, such as documentation, would no longer apply to the Aachen company, says Kurz. Strictly speaking, Biothrust is a “machine supplier”. The founders do need CE certification that confirms the EU requirements for safety and medical purposes. With the capital from Thelen and grants from the Exist funding program, they now want to implement their first pilot projects with cell culture producers and build their team around biotechnologists, engineers and sales people. In the near future, the production of sustainable laboratory meat may not be far away.

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