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Stem Cell Research

Direct neuronal reprogramming: A promising method for targeted generation of neurons from the brain's own non-neuronal cells after loss

Scientists from Helmholtz Zentrum München and the Biomedical Center of the LMU have made a crucial step towards fighting neuronal loss. They developed a methodology which allows turning local brain cells into new neurons after brain injury. This approach alleviates the need for transplantation and immunosuppression. This work has been published in Neuron.

Reprogrammed neurons in different tonality of grey. © Dr. Riccardo Bocchi, Institute of Stem Cell Research, Helmholtz Zentrum München.

Neurons that are lost in neurodegenerative disease or after brain injury can so far not be replaced. This often leads to permanent deficits. Even though cell transplantation has achieved promising improvement for Parkinson disease patients, it requires brain surgery and immunosuppression inhibiting the activity of the immune system and hence reducing the ability to fight infections and other diseases.

The pioneering work from the group of Prof. Magdalena Götz from Helmholtz Zentrum München and the Biomedical Center at Ludwig-Maximilians-University Munich (LMU) thus developed an approach using local brain cells to generate new neurons, the so-called ‘direct reprogramming’. The Götz lab has first tested this in the culture dish in 2002 and were very excited to find that young glial cells can be converted into neurons using factors that are active in development, when neurons are generated. They then moved on to adapt this approach in a mouse model of traumatic brain injury in 2005 (Buffo et al., 2005) and have recently reported to achieve an amazing efficiency in this conversion process after brain injury (Gascon et al., 2015). Now they tackled the next key question – namely how many specific types of neurons can be generated – as brain function depends on zillions of different nerve cells.

“Here we show that astrocytes*, located at different layer positions in the brain can be reprogrammed into different neuronal subtypes after brain injury. We were amazed to find that glial cells in different layers can be converted into neurons with the correct layer identity and connecting to other brain regions. While this is a great step forward in generating new neuronal subtypes, we still need to understand how this works”, says Magdalena Götz.

This approach offers the long-term perspective to replace neurons that have been lost after acute injuries, such as trauma or stroke, as well as in neurodegenerative diseases. The pioneering results obtained in this study may also be applicable to other brain regions affected in different disease conditions.

“We are convinced that these finding have a great impact in the field of stem cell research and regenerative medicine, given the surprising results and important therapeutic implications”, says Dr. Riccardo Bocchi from Götze’s Research Group Neural Stem Cells.
The Götz lab now aims to further develop this exciting approach in many aspects, including improving the mode of delivery of the reprogramming factors, exploring the functional integration of the new neurons and converting glial cells from the human brain into new neurons.

Further information
*Astrocytes are the most common representatives of glial cells, whose main function is to form the supporting tissue in the central nervous system of mammals.

Original publication:
Mattugini, Bocchi et al., 2019: Inducing different neuronal subtypes from astrocytes in the injured mouse cerebral cortex. Neuron, DOI: 10.1016/j.neuron.2019.08.009

TheInstitute of Stem Cell Research (ISF) investigates the basic molecular and cellular mechanisms of stem cell maintenance and differentiation. From that, the ISF then develops approaches in order to replace defect cell types, either by activating resting stem cells or by re-programming other existing cell types to repair themselves. The aim of these approaches is to stimulate the regrowth of damaged, pathologically changed or destroyed tissue.

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,500 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 19 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

As one of Europe's leading research universities, LMU Munich is committed to the highest international standards of excellence in research and teaching. Building on its 500-year-tradition of scholarship, LMU covers a broad spectrum of disciplines, ranging from the humanities and cultural studies through law, economics and social studies to medicine and the sciences. 15 percent of LMU‘s 50,000 students come from abroad, originating from 130 countries worldwide. The know-how and creativity of LMU's academics form the foundation of the University's outstanding research record. This is also reflected in LMU‘s designation of as a "university of excellence" in the context of the Excellence Initiative, a nationwide competition to promote top-level university research.