Electrical stimulation helps organoids mature

Researchers in the Mina Gouti lab show in ​“Advanced Science” that electrical pulse stimulation helps human neuromuscular organoids mature. This non-invasive approach may make it possible to use organoid models to study adult-onset diseases and to gain a better understanding of how tissues mature.

 

Organoids more faithfully recapitulate the three-dimensional (3D) organization of human tissues, thus serving as powerful models for scientists to investigate human disease. However, as yet, they do not fully mature in culture. As a result, studying adult on-set diseases such as Amyotrophic Lateral Sclerosis and muscular dystrophies using these models remains challenging. 

Researchers from the Stem Cell Modeling of Development and Disease lab of Dr. Mina Gouti at the Max Delbrück Center, led by first author Dr. Chrysanthi-Maria Moysidou, a Marie Skłodowska-Curie Postdoctoral Fellow, have now developed a non-invasive and non-destructive approach to promote human neuromuscular organoid maturation using electrical pulse stimulation (EPS). The technique was published in the journal ​“Advanced Science.” 

“Our findings demonstrate that bioelectrical cues are powerful regulators of organoid maturation and provide a simple, non-invasive strategy to generate more physiologically relevant human organoids for disease modeling and regenerative medicine,” says Moysidou.

 

Importantly, the scientists found that low-frequency EPS had to be applied during a critical window of neuromuscular development to successfully stimulate organoids to mature. EPS treated organoids had more mature neural networks, larger muscle fibers, and stronger muscle contractions, which are characteristics of more mature tissues. 

The researchers also found that the duration of stimulation was critical. ​“Our results show that prolonged application of electrical pulses more effectively promotes maturation than short time frames,” adds Moysidou. These improvements also persisted after stimulation had been stopped, suggesting a long-lasting developmental imprint.

 

Implications for research

The work holds promise to advance in the study of neuromuscular diseases. ​“We anticipate that the versatility of this approach will enable broader applications, facilitating the morphological and functional maturation of diverse organoid systems as human-relevant models of physiology and disease,” says Gouti, senior author of the paper. 

The proof-of-principle study was conducted by generating organoids from two different genetic backgrounds. Next, the group will test the approach across organoids with a wider range of genetic and tissue diversity, and will use bioengineering approaches to develop user-friendly and high-throughput compatible EPS platforms, to fully realize the potential of this technology. 

“As organoid technologies continue to evolve, a multi-disciplinary approach that integrates developmental biology, bioengineering, quantitative imaging, and AI will be essential to build increasingly predictive human tissue models,” Gouti adds. 

The work was supported by the European Research Council (ERC) and the Horizon Europe Marie Sklodowska-Curie Actions, Individual Postdoctoral Fellowship programme.

 

Further information

 

Contacts

Dr. Chrysanthi-Maria Moysidou
Stem Cell Modeling of Development and Disease lab
Max Delbrück Center
chrysanthimoysidou@​gmail.​com

Prof. Dr. Mina Gouti
Stem Cell Modeling of Development and Disease lab
Max Delbrück Center
mina.​gouti@​mdc-​berlin.​de

Gunjan Sinha
Editor, Communications
Max Delbrück Center
+49 30 9406 – 2118
presse@​mdc-​berlin.​de 

 

 

 

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