Whole and fractionated human platelet lysate biomaterials-based biotherapy induces strong neuroprotection in experimental models of amyotrophic lateral sclerosis

Flore Gouel, Kelly Timmerman, Philippe Gosset, Cedric Raoul, Mary Dutheil, Aurélie Jonneaux, Guillaume Garçon, Caroline Moreau, Veronique Danel-Brunaud, James Duce, Thierry Burnouf, Jean Christophe Devedjian, David Devos

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1 引文 斯高帕斯(Scopus)

摘要

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease of motor neurons leading to death within 3 years and without a curative treatment. Neurotrophic growth factors (NTFs) are pivotal for cell survival. A reason for the lack of patient efficacy with single recombinant NTF brain infusion is likely to be due to the synergistic neuroprotective action of multiple NTFs on a diverse set of signaling pathways. Fractionated (protein size <50, <30, <10, <3 kDa) heat-treated human platelet lysate (HHPL) preparations were adapted for use in brain tissue with the aim of demonstrating therapeutic value in ALS models and further elucidation of the mechanisms of action. In neuronal culture all fractions induced Akt-dependent neuroprotection as well as a strong anti-apoptotic and anti-ferroptotic action. In the <3 kDa fraction anti-ferroptotic properties were shown to be GPX4 dependent highlighting a role for other platelet elements associated with NTFs. In the SOD1G86R mouse model, lifespan was strongly increased by intracerebroventricular delivery of HHPL or by intranasal administration of <3 kDa fraction. Our results suggest that the platelet lysate biomaterials are neuroprotective in ALS. Further studies would now validate theragnostic biomarker on its antiferroptotic action, for further clinical development.

原文英語
文章編號121311
期刊Biomaterials
280
DOIs
出版狀態已發佈 - 1月 2022

ASJC Scopus subject areas

  • 生物物理學
  • 生物工程
  • 陶瓷和複合材料
  • 生物材料
  • 材料力學

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