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Human induced pluripotent stem cells: A game-changer for drug testing

Researchers at the Fraunhofer Institute for Biomedical Engineering IBMT have developed innovative solutions for the production and preservation of human induced pluripotent stem (hiPS) cells, potentially revolutionising drug discovery and toxicity testing processes.

The challenge of translating in vitro results

Many promising drug candidates fail during clinical trials due to unexpected serious side effects, despite successful lab tests involving cell cultures. This discrepancy often stems from the use of animal tissue in preliminary testing, which may not accurately predict human responses.

hips bioreactor

In vitro pharmacological and toxicological screening involving neural cells. © Fraunhofer IBMT / Bernd Müller

hiPS cells: A more reliable model

hiPS cells, derived from human tissue, offer a more precise basis for predicting drug efficacy and safety in humans. These cells can be reprogrammed and differentiated into various cell types found in the human body, significantly reducing the risk of unforeseen side effects in clinical trials.

Dr Julia Neubauer, head of the Cryo & Stem Cell Technologies department at Fraunhofer IBMT, and her team have made significant strides in multiplying and differentiating hiPS cells in bioreactors.

“It is now possible for the first time to scale up the process so large quantities of functional cells are created in a short time,” Dr Neubauer says. The researchers developed a specialised elastic hydrogel substrate for the bioreactor, mimicking the natural environment of the cells. This innovation allows for the production of billions of
cells suitable for medical testing.

Cryopreservation breakthrough

Addressing the challenges of storage and availability, the Fraunhofer team has developed unique cryopreservation methods. These techniques involve:

• Rapid cooling using liquid nitrogen
• Specially designed cell culture plates
• Freezing media to prevent ice crystal formation

Liquid nitrogen is used to cool the cell models grown in the bioreactor from about plus 23 degrees Celsius down to minus 196 degrees within two seconds. The special cell culture plate that can be used to first culture the cells and then freeze them. Combined with the rapid freezing process, special freezing media impair the formation of ice crystals in the cell tissue, which would damage the material and leave it mushy.

“If you’ve ever frozen strawberries at home, you’ll be familiar with this undesired effect,” Neubauer explains, referring to the damage caused by ice crystals.

The team has created a detailed cryopreservation protocol, ensuring the specific types of cells retain full functionality after thawing.

Implications for drug development

These advancements in bioreactor and cryostorage technologies pave the way for more efficient use of hiPS cells in medical research. By replacing traditional in vitro tests and animal testing with more accurate human cell-based systems, the drug development process can become more efficient and safer.

“On the whole, the accomplishments of R2U-Tox-Assay enable more efficient, safe development of drug candidates to treat a range of diseases, including heart and eye diseases and even neurological disorders such as dementia,” Dr Neubauer says.

The project, which recently concluded, was a collaboration between Fraunhofer IBMT, Janssen Pharmaceutica N.V., and the Institute for Bioengineering of Catalonia. It received funding as an innovation project under the EU’s EIT Health initiative.