News and publications


PREMSTEM researchers are highlighted as bold

miR-146b Protects the Perinatal Brain against Microglia-Induced Hypomyelination

Cindy Bokobza, Pooja Joshi, Anne-Laure Schang, Zsolt Csaba, Valérie Faivre, Amélie Montané, Anne Galland, Anouk Benmamar-Badel, Emmanuelle Bosher, Sophie Lebon, Leslie Schwendimann, Shyamala Mani, Pascal Dournaud, Valerie Besson, Bobbi Fleiss, Pierre Gressens, Juliette Van Steenwinckel 

Ann Neurol. (2021);

Received: 7 May 2020 / Accepted: 3 November 2021 / Available online: 5 November 2021

In the preterm newborn, perinatal inflammation mediated by microglia contributes significantly to neurodevelopmental injuries including white matter injury (WMI). This study demonstrates that miR-146b acts as a negative feedback mechanism against inflammatory activation specifically in microglia in a model of WMI, demonstrating that miR mediated therapies may have a future as efficient strategies to protect the developing brain against WMI.

The immune-inflammatory response of oligodendrocytes in a murine model of preterm white matter injury: the role of TLR3 activation

Marta Boccazzi, Juliette Van Steenwinckel, Anne-Laure Schang, Valérie Faivre, Tifenn Le Charpentier, Cindy Bokobza, Zsolt Csaba, Claudia Verderio, Marta Fumagalli, Shyamala Mani and Pierre Gressens

Cell Death Dis 12, 166 (2021);

Received: 2 June 2020 / Revised: 13 December 2020 / Accepted: 3 January 2021 / Available online: 8 February 2021

This study focused on toll-like receptor-3, a protein activated by double-strand RNA, which promotes neuroinflammation. The aim was to better understand its expression and role in oligodendrocytes (one of the last types of cell to form in the brain). The in vivo mouse model mimicked white matter injury occurring in preterm babies.

Therapeutic potential of stem cells for preterm infant brain damage: can we move from the heterogeneity of preclinical and clinical studies to established therapeutics?

Sofia Passera, Marta Boccazzi, Cindy Bokobza, Valerie Faivre, Fabio Mosca, Juliette Van Steenwinckel, Monica Fumagalli, Pierre Gressens and Bobbi Fleiss

Biochemical Pharmacology 2021, 114461;

Received: 10 December 2020 / Revised: 27 January 2021 / Accepted: 2 February 2021 / Available online: 8 February 2021

In this review, the researchers summarise and discuss preclinical and clinical investigations which have studied stem cells as an effective neuroprotectant for perinatal brain injury.


Microglia-Mediated Neurodegeneration in Perinatal Brain Injuries

Bobbi Fleiss, Juliette Van Steenwinckel, Cindy Bokobza, Isabelle K. Shearer, Emily Ross-Munro and Pierre Gressens

Biomolecules 2021, 11(1), 99;

Received: 29 November 2020 / Revised: 8 January 2021 / Accepted: 11 January 2021 / Published: 13 January 2021

This review looks at strategies developed experimentally to modulate microglia and reduce brain injury in babies. It focusses on four causes of perinatal brain injury which occur frequently in both westernised and emerging countries, including EoP and neonatal stroke, and reviews pharmacological approaches as well as novel nanoparticle mediated therapies.

Neuroprotection offered by mesenchymal stem cells in perinatal brain injury: Role of mitochondria, inflammation, and reactive oxygen species

Syam Nair, Eridan Rocha-Ferreira, Bobbi Fleiss, Cora H Nijboer, Pierre Gressens, Carina Mallard, Henrik Hagberg

Journal of Neurochemistry 2021, 2021;158:59–73; 

Received: 15 July 2020 / Revised: 3 December 2020 / Accepted: 3 December 2020 / Published: 12 December 2020

This review summarises the present state, the underlying causes, challenges and possibilities for effective clinical translation of mesenchymal stem cell therapy.

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Reduce Neuroinflammation, Promote Neural Cell Proliferation and Improve Oligodendrocyte Maturation in Neonatal Hypoxic-Ischemic Brain Injury

Nicole Kaminski, Christian Köster, Yanis Mouloud, Verena Börger, Ursula Felderhoff-Müser, Ivo Bendix, Bernd Giebel and Josephine Herz

Front. Cell. Neurosci. 2020, 14:601176
Received: 31 August 2020 / Accepted: 19 November 2020 / Published: 10 December 2020
This study investigated the impact of MSC-EVs on neonatal HI-induced brain injury, demonstrating that MSC-EVs mediate anti-inflammatory effects, promote regenerative responses and improve key developmental processes in the injured neonatal brain.

A Model of Germinal Matrix Hemorrhage in Preterm Rat Pups

Masako Jinnai, Gabriella Koning, Gagandeep Singh-Mallah, Andrea Jonsdotter, Anna-Lena Leverin, Pernilla Svedin, Syam Nair, Satoru Takeda, Xiaoyang Wang, Carina Mallard, Carl Joakim Ek, Eridan Rocha-Ferreira and Henrik Hagberg 

Front. Cell. Neurosci. 2020, 14:535320;
Received: 15 February 2020 / Accepted: 5 November 2020 / Published: 3 December 2020
This study aimed to develop and characterise a model of severe germinal matrix hemorrhage (GMH) corresponding to brain maturation in preterm human infants and at an age when the germinal matrix is still present, and to further characterise the pathophysiology of this disease with the hope of assisting novel experimental therapy studies.

Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key

Daan R.M.G. Ophelders, Ruth Gussenhoven, Luise Klein, Reint K. Jellema, Rob J.J. Westerlaken, Matthias C. Hütten, Jeroen Vermeulen, Guido Wassink, Alistair J. Gunn and Tim G.A.M. Wolfs

Cells 20209(8), 1871;
Received: 8 June 2020 / Revised: 31 July 2020 / Accepted: 5 August 2020 / Published: 10 August 2020
This review underlines the importance of employing the right combination of interventions at the right time to support optimal neurodevelopmental outcomes.

Cortical Gray Matter Injury in Encephalopathy of Prematurity: Link to Neurodevelopmental Disorders

Bobbi Fleiss, Pierre Gressens and Helen B. Stolp

Front. Neurol. 2020, 11:575;
Received: 7 April 2020 / Accepted: 19 May 2020 / Published: 14 July 2020