Nasal administration of mesenchymal stem cells reverses chemotherapy-induced peripheral neuropathy in mice

Nabila Boukelmoune, Geoffroy Olivier Laumet, Yongfu Tang, Jiacheng Ma, Itee Mahant, Susmita K. Singh, Cora Nijboer, Manon Benders, Annemieke Kavelaars, Cobi J. Heijnen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequently reported adverse effects of cancer treatment. CIPN often persists long after treatment completion and has detrimental effects on patient's quality of life. There are no efficacious FDA-approved drugs for CIPN. We recently demonstrated that nasal administration of mesenchymal stem cells (MSC) reverses the cognitive deficits induced by cisplatin in mice. Here we show that nasal administration of MSC after cisplatin- or paclitaxel treatment- completely reverses signs of established CIPN, including mechanical allodynia, spontaneous pain, and loss of intraepidermal nerve fibers (IENF) in the paw. The resolution of CIPN is associated with normalization of the cisplatin-induced decrease in mitochondrial bioenergetics in DRG neurons. Nasally administered MSC enter rapidly the meninges of the brain, spinal cord and peripheral lymph nodes to promote IL-10 production by macrophages. MSC-mediated resolution of mechanical allodynia, recovery of IENFs and restoration of DRG mitochondrial function critically depends on IL-10 production. MSC from IL-10 knockout animals are not capable of reversing the symptoms of CIPN. Moreover, WT MSC do not reverse CIPN in mice lacking IL-10 receptors on peripheral sensory neurons. In conclusion, only two nasal administrations of MSC fully reverse CIPN and the associated mitochondrial abnormalities via an IL-10 dependent pathway. Since MSC are already applied clinically, we propose that nasal MSC treatment could become a powerful treatment for the large group of patients suffering from neurotoxicities of cancer treatment.

Original languageEnglish (US)
Pages (from-to)43-54
Number of pages12
JournalBrain, behavior, and immunity
Volume93
DOIs
StatePublished - Mar 2021

Keywords

  • Cisplatin
  • Interleukin-10 (IL-10)
  • Meninges
  • Mesenchymal Stem Cells (MSC)
  • Mitochondria
  • Peripheral neuropathy
  • Sensory neurons

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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