Modern studies suggest that Mesenchymal stem cells (MSCs) when administered intravenously, can cross the blood-brain barrier (BBB) leading to various regenerative effects.
Do mesenchymal stem cells administered via IV cross the blood-brain barrier (BBB)?
Mesenchymal stem cells (MSCs) intrinsically possess unique features that help them migrate towards areas of inflammation. MSCs secrete various types of secretomes to induce nerve regeneration and pain-relieving effects at inflammatory sites. Modern studies suggest that Mesenchymal stem cells (MSCs) when administered intravenously, can cross the blood-brain barrier (BBB) leading to various regenerative effects. This was confirmed by a recent study conducted by Kim et al. which found that MSCs administered intravenously crossed the BBB and migrated into the brain in a mouse model for Alzheimer’s Disease. (3)
What is the blood-brain barrier?
The blood-brain barrier (BBB) is a dispersion barrier, which prevents the entry of most compounds from the blood to the brain. According to Ballabh, the barrier is highly particular, meaning it only allows certain substances to cross from the bloodstream into the brain. This protects the brain from toxins that can potentially damage neurons.
Stem cells cross the blood-brain barrier in an animal stroke model
Mesenchymal stem cells represent a great potential to reverse neuronal damage associated with CNS diseases such as Multiple Sclerosis, Parkinson’s disease (PD), and Alzheimer’s disease (AD). (4)
A study conducted by Yilmaz et al. found that intravenously (IV) injected mesenchymal stem cells (MSCs) can travel through the blood-brain barrier to the cerebral artery occlusion (t-MCAO) model for stroke. (5) The brain tropism (movement into the brain) of MSCs was confirmed by whole-body imaging of radiolabeled (visible radioactive compound) MSCs given to rats. During the first two hours after stroke, MSCs transiently pass through the lungs and continued to migrate over time within the region of brain ischemia, crossing the blood-brain barrier. The study concluded through the use of whole-body imaging that mesenchymal stem cells (MSCs), when administered intravenously were able to populate the CNS after passing through the BBB. (5)
What makes mesenchymal stem cells (MSCs) so special?
Mesenchymal stem cells (MSCs) are an especially attractive therapeutic agent due to their ease of isolation, established safety, and potential to target multiple pathways involved in neuronal regeneration.
MSCs are widely used in the treatment of various diseases due to their self-renewable, differentiation, anti-inflammatory, and immunomodulatory properties. In-vitro (performed in a laboratory setting) and in-vivo (taking place in a living organism) studies have supported the understanding mechanisms, safety, and efficacy of MSC therapy in clinical applications. (6)
Do mesenchymal stem cells get trapped in the lungs?
Studies suggest that pulmonary trapping of stem cells following intravenous administration is only a transient phenomenon, meaning the cells eventually pass through reaching other areas of the body (11). Physical size plays an important role in the migratory capabilities of any cell throughout the body. (see figure below). The size of cells can result in entrapment in certain areas resulting in a loss of migratory abilities. Mesenchymal stem cells (MSCs) can range in size depending on their original source (bone marrow, adipose tissue, cord blood or umbilical cord tissue). Importantly, endogenous MSCs are smaller in size (∼10 μm), which enable efficient trafficking via systemic circulation (10). According to a 2009 study conducted by Majore et al. the average diameter of a single cord tissue-derived mesenchymal stem cell is roughly 11 μm (similar in size to a white blood cell) (9). Mesenchymal stem cells also undergo a process called cellular deformability, which can facilitate passage of larger cells through smaller vessels (10). This data suggests that MSCs can bypass the pulmonary ‘first-pass effect’ (becoming trapped in the lungs) leading to efficient circulation throughout the entire body, including the CNS.
