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

Abstract

Neurological disorders are a leading cause of morbidity worldwide, giving rise to a growing need to develop treatments to revert their symptoms. This review highlights the great potential of recent advances in cell therapy for the treatment of neurological disorders. Through the administration of pluripotent or stem cells, this novel therapy may promote neuroprotection, neuroplasticity, and neuroregeneration in lesion areas. The review also addresses the administration of these therapeutic molecules by the intranasal route, a promising, non-conventional route that allows for direct access to the central nervous system without crossing the blood–brain barrier, avoiding potential adverse reactions and enabling the administration of large quantities of therapeutic molecules to the brain. Finally, we focus on the need to use biomaterials, which play an important role as nutrient carriers, scaffolds, and immune modulators in the administration of non-autologous cells. Little research has been conducted into the integration of biomaterials alongside intranasally administered cell therapy, a highly promising approach for the treatment of neurological disorders.

Rapid and Widespread Distribution of Intranasal Small Extracellular Vesicles Derived from Mesenchymal Stem Cells throughout the Brain Potentially via the Perivascular Pathway

“…For example, the nasal anatomy of humans is different from that of rodents. The olfactory epithelium serves as the main facilitator for the transfer of molecules to the brain and covers only 3% of the nasal cavity in humans, compared to 50% in rodents [42]. In addition, mild anesthesia may lower the velocity of inhaled droplets and increase contact with the nasal mucosa [13].…”

Plausible Role of Stem Cell Types for Treating and Understanding the Pathophysiology of Depression

“…Stem cells therapy has crucial clinical properties in the treatment of disorders associated with CNS. One of the major obstacles in the delivery of stem cells or any type of drug into the CNS is the blood brain barrier (BBB) [ 67 , 68 ]. The use of stereotactic or intrathecal injections is usually necessary for stem cell therapy in the brain.…”

“…INA is preferable over the intravenous administration in a number of ways: (1) it delivers therapeutic agents to the CNS to a large extent; (2) it manages to avoid first-pass metabolism; (3) it is noninvasive and simple to use, allowing for repeated administration if required; and (4) its side effects are reduced since no other healthy organs are exposed to the therapeutic agent [ 67 ]. The intranasal injection of neural stem cells (NSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) have been used in the treatment of various neurological disorders [ 68 ]. The INA of MSCs have been widely used in the research and treatment of glioma, neurodegeneration, and brain injury.…”

“…Adult somatic cells have been transformed genetically to an embryonic stem (ES) cell-like state through enforced genetic expression and proteins crucial for preserving the defining traits of ES cells, resulting in iPSCs [ 68 ]. Human iPSCs (hiPSCs) allow for the recreation of cellular phenotypes, typically in depression and the search for new antidepressant treatments.…”

The Optimization Design of Macrophage Membrane Camouflaging Liposomes for Alleviating Ischemic Stroke Injury through Intranasal Delivery

“…Due to the unique anatomical structure of the nasal cavity, drugs can be absorbed through the nose and transported to the brain [ 45 ]. Intranasal administration can bypass the blood–brain barrier and directly reach the central nervous system through the olfactory and trigeminal pathways [ 46 , 47 ]. Intranasal administration has advantages such as non-invasiveness, safety, and speed [ 48 ].…”