Intranasal delivery of stem cell-based therapies for the treatment of brain malignancies

Abstract

Introduction Glioblastoma (GBM) is the most aggressive malignant brain cancer in adults, and its poor prognosis and resistance to the existing standard of care require the development of innovative therapeutic modalities. The local delivery of stem cells as therapeutic carriers against glioma has produced encouraging results, but encounters obstacles with regards to the repeatability and invasiveness of administration. Intranasal delivery of therapeutic stem cells could overcome these obstacles, among others, as a noninvasive and easily repeatable mode of administration. Areas covered This review describes nasal anatomy, routes of stem cell migration, and factors affecting stem cell delivery to hard-to-reach tumors. Furthermore, this review discusses the molecular mechanisms underlying stem cell migration following delivery, as well as possible stem cell effector functions to be considered in combination with intranasal delivery. Expert opinion Further research is necessary to elucidate the dynamics of stem cell effector functions in the context of intranasal delivery and optimize their therapeutic potency. Nonetheless, the technique represents a promising tool against brain cancer and has the potential to be expanded for use against other brain pathologies.

Optimizing Stem Cell Therapy after Ischemic Brain Injury

“…SPECT imaging has the added benefit of a lower false-positive signaling compared to MRI. 27,183 Near-infrared (NIR) fluorescence imaging is advantageous over conventional fluorescence imaging due to its improved ability to penetrate tissues. NIR fluorescence imaging was shown to visualize and track the in vivo tumor-targeting process and tissue distribution of intravenously injected MSCs.…”

“…However, they do not provide anatomical information and must be used in conjunction with MRI, computerized tomography, or X-ray. SPECT imaging has the added benefit of a lower false-positive signaling compared to MRI [ 27 , 183 ].…”

“…7,[22][23][24][25] Transplanted stem cells can also be used as delivery vectors for agents such as chemotherapeutics, pro-drugs, and cytokines that can mediate inflammatory responses. [26][27][28] Despite the disappointing randomized controlled trial results, stem cell therapy remains a highly promising method to treat ischemic brain injury. Ischemic brain injury is defined as any injury to the brain caused by oxygen deprivation, such as ischemic stroke, perinatal hypoxic-ischemic encephalopathy (HIE), and cerebral ischemia secondary to cardiac arrest.…”

Nose ‐To ‐Brain Delivery of Mitochondria for Treatment of Parkinson’s Disease Model Rats With 6-Hydroxydopamine

“…In situ or intravenous injection of naked mitochondria isolated from healthy cells has successfully restored mitochondrial function, with subsequent improvement of mobility in neurotoxin-induced rat models of PD [8,9], but the feasibility and e cacy of intranasal adminstration of mitochondria, a relatively fast, safe approach are unknown. However, studies have demonstrated that stem cells delivered intranasally entered the CNS [10] and have been used in treatment of PD [11] and malignant brain tumours [12].…”

The effect of intranasally administered TLR3 agonist larifan on metabolic profile of microglial cells in rat with C6 glioma

“…Intranasal route is conside red as an alternative way. This route has a number of advantages: BBB ceases to be an obstacle, the method is noninvasive and is easily repeatable [15,16]. This study was aimed to investigate the effect of intranasally delivered TLR3 agonist Larifan on microglial cell metabolic profile in rats with C6 glioma.…”