Intranasal Administration of Undifferentiated Oligodendrocyte Lineage Cells as a Potential Approach to Deliver Oligodendrocyte Precursor Cells into Brain

Abstract

Oligodendrocyte precursor cell (OPC) migration is a mechanism involved in remyelination; these cells migrate from niches in the adult CNS. However, age and disease reduce the pool of OPCs; as a result, the remyelination capacity of the CNS decreases over time. Several experimental studies have introduced OPCs to the brain via direct injection or intrathecal administration. In this study, we used the nose-to brain pathway to deliver oligodendrocyte lineage cells (human oligodendroglioma (HOG) cells), which behave similarly to OPCs in vitro. To this end, we administered GFP-labelled HOG cells intranasally to experimental animals, which were subsequently euthanised at 30 or 60 days. Our results show that the intranasal route is a viable route to the CNS and that HOG cells administered intranasally migrate preferentially to niches of OPCs (clusters created during embryonic development and adult life). Our study provides evidence, albeit limited, that HOG cells either form clusters or adhere to clusters of OPCs in the brains of experimental animals.

In Vitro Effects of Methylprednisolone over Oligodendroglial Cells: Foresight to Future Cell Therapies

“…In this study, we used a culture of HOG cells, which are human oligodendrocyte lineage precursor cells from an oligodendroglioma line. Previous studies by our group and other researchers have shown that these cells behave similarly to OPCs, expressing markers of precursor cells and of the oligodendrocyte lineage [47]. Given their ability to proliferate and differentiate to express PLP, MBP, and MOG and to generate myelin [48,49], these cells have been used in research on the mechanisms of myelination [48][49][50][51][52] and the influence of the immune system over OPCs [53][54][55].…”

Chances and challenges in intranasal administration delivery for brain disease treatment

“…To advance our understanding, additional multimodal imaging technologies are needed for studying brain cell uptake and the real-time localization of drugs. [33][34][35][36] (3) In-depth investigation of interactions between nanodelivery systems, drug formulation, and neural pathways: The precise mechanism by which drugs enter the brain through INA delivery systems remains unclear. Combining in-silico modeling of the intranasal environment with experimental studies on drug-nanocarrier interactions and their interactions with cells can provide valuable insights for the rational design of drug delivery systems.…”

“…(2) Multimodal real‐time tracing system for precise assessment of INA delivery efficiency: Currently, the quantification of INA delivery efficiency primarily relies on mathematical modeling and tomographic slices. To advance our understanding, additional multimodal imaging technologies are needed for studying brain cell uptake and the real‐time localization of drugs 33–36 …”

Nose-to-Brain: The Next Step for Stem Cell and Biomaterial Therapy in Neurological Disorders

“…After reaching the CNS, cells were able to differentiate into NG2 + oligodendrocyte precursor cells (OPC), mature oligodendrocytes, astrocytes, and neurons [37]. Gómez-Pinedo et al [38] used the intranasal route to administer oligodendrocyte-lineage cells, which reached the olfactory bulb and migrated to areas with quiescent endogenous OPCs (fimbria, corpus callosum, and septum); this was one of the first studies to use this cell lineage for intranasal administration.…”