Stem cell delivery of therapies for brain disorders

Abstract

The blood brain barrier (BBB) poses a problem to deliver drugs for brain malignancies and neurodegenerative disorders. Stem cells such as neural stem cells (NSCs) and mesenchymal stem cells (MSCs) can be used to delivery drugs or RNA to the brain. This use of methods to bypass the hurdles of delivering drugs across the BBB is particularly important for diseases with poor prognosis such as glioblastoma multiforme (GBM). Stem cell treatment to deliver drugs to neural tumors is currently in clinical trial. This method, albeit in the early phase, could be an advantage because stem cells can cross the BBB into the brain. MSCs are particularly interesting because to date, the experimental and clinical evidence showed ‘no alarm signal’ with regards to safety. Additionally, MSCs do not form tumors as other more primitive stem cells such as embryonic stem cells. More importantly, MSCs showed pathotropism by migrating to sites of tissue insult. Due to the ability of MSCs to be transplanted across allogeneic barrier, drug‐engineered MSCs can be available as off‐the‐shelf cells for rapid transplantation. This review discusses the advantages and disadvantages of stem cells to deliver prodrugs, genes and RNA to treat neural disorders.

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

“…It was evidenced by PCR detection of the human albumin gene in rats receiving HUCBMSCs. These findings were in accordance with Aleynik et al [68] who reported stem cell homing to the brain. So, they can be the future form of treatment to bypass the blood brain barrier.…”

Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy

“…Specifically, they show migration towards pathology sites such as tumours/neurodegeneration (termed 'pathotropism') [8,9]. Intravenously delivered NSCs can cross the blood-brain barrier surrounding neural tissue into pathology foci -a phenomenon modulated by inflammation, astrocytosis and blood vessel formation -minimising adverse effects in surrounding normal host tissue [10].…”

Stem cell treatment for age-related neurodegenerative diseases

“…Further studies examining the effectiveness of stem cells overexpressing various growth factors to reduce degeneration neurons and improve clinical outcomes will help to maximize the positive effects of cell therapy. Furthermore, the affinity for stem cells, especially MSCs, to migrate to the brain make them attractive for gene and drug delivery [56]. In clinics, although the use of stem cell therapy for neurodegenerative diseases has gained considerable momentum in the recent past, there are still numerous hurdles that must be overcome.…”