Mesenchymal Stem Cell (MSC)-Based Drug Delivery into the Brain across the Blood–Brain Barrier

Abstract

At present, stem cell-based therapies using induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) are being used to explore the potential for regenerative medicine in the treatment of various diseases, owing to their ability for multilineage differentiation. Interestingly, MSCs are employed not only in regenerative medicine, but also as carriers for drug delivery, homing to target sites in injured or damaged tissues including the brain by crossing the blood–brain barrier (BBB). In drug research and development, membrane impermeability is a serious problem. The development of central nervous system drugs for the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, remains difficult due to impermeability in capillary endothelial cells at the BBB, in addition to their complicated pathogenesis and pathology. Thus, intravenously or intraarterially administered MSC-mediated drug delivery in a non-invasive way is a solution to this transendothelial problem at the BBB. Substances delivered by MSCs are divided into artificially included materials in advance, such as low molecular weight compounds including doxorubicin, and expected protein expression products of genetic modification, such as interleukins. After internalizing into the brain through the fenestration between the capillary endothelial cells, MSCs release their cargos to the injured brain cells. In this review, I introduce the potential and advantages of drug delivery into the brain across the BBB using MSCs as a carrier that moves into the brain as if they acted of their own will.

Current Strategies and Therapeutic Applications of Mesenchymal Stem Cell-Based Drug Delivery

“…MSCs are adult stem cells known for their ability to self-renew and differentiate into various cell lineages, making them valuable for regenerative medicine and drug delivery applications [2,29,30]. These capabilities allow MSCs to be engineered to enhance their survival, retention, migration, and growth factor production, which are essential for effective drug delivery [7]. Additionally, MSCs can be loaded with therapeutic agents and used for tissue regeneration and cancer therapeutics without compromising their differentiation potential [2,30].…”

“…Stem cell-based drug delivery systems include innovative approaches such as stem cell membrane-coated nanoparticles (SCMNPs), stem cell-derived extracellular vesicles (EVs), stem cell-laden scaffolds, and scaffold-free stem cell sheets [6]. These strategies hold significant promise as novel approaches for skin regeneration and wound healing by addressing challenges such as optimal source selection, processing methods, administration techniques, and cell survival at wound sites [1,7,8]. These strategies leverage the self-renewal and differentiation capabilities of MSCs to accelerate wound closure, promote skin regeneration, and prevent scarring.…”

Non-Invasive Device-Mediated Drug Delivery to the Brain across the Blood–Brain Barrier

“…On the other hand, mesenchymal stem cells (MSCs) [ 45 ] administered through intravenous or intracarotid routes can be utilized as a drug carrier, homing to the target sites, although they are often clinically used for regenerative medicine due to their differentiation potential [ 46 ]. Toshihiko Tashima proposes MSC-based drug delivery into the brain across the BBB [ 47 ]. The substances delivered by MSCs are divided into artificially included materials in advance, such as low-molecular-weight compounds including doxorubicin, and the expected protein expression products of genetic modification, such as interleukins.…”