Mesenchymal Stem Cells and the Blood-Brain Barrier

Mesenchymal stem cells are adult cells which have the ability to cross the blood brain barrier (BBB) when administered intravenously. These cells have natural traits that allow them to move toward areas with inflammation.

MSCs release different substances that help nerves heal and reduce pain in those areas. Research including a study by Kim shows that if MSCs are injected through a vein, they can pass through the BBB — demonstrated in a mouse model for Alzheimer's disease, showing their potential to help regenerate brain tissue.

The important protective layer around the brain and spinal cord is known as the blood brain barrier — a concept explored further on our science page. With the help of this shield, it is not easy for harmful substances to enter the brain. Brain endothelial cells cover the blood vessels in the brain and stick tightly to each other through special connections called junctional adhesion molecules, forming a strong barrier.

The BBB needs vascular endothelial growth factor (VEGF) to form and work properly — a protein that helps build and maintain the cells lining the tiny blood vessels in the brain. The BBB stops many immune cells, such as white blood cells and T cells, from entering the brain, keeping it safe from swelling and harm.

Circumventricular organs are areas of the brain where the BBB is weaker and some substances pass through more easily. Fat-soluble substances can cross the BBB, while essential amino acids need special transport systems. The cerebrospinal fluid (CSF) also plays a role — acting as a cushion around the brain and spinal cord, and helping clean up waste, kept separate from blood by its own specialised barrier cells.

Sometimes brain tumors or strokes can disrupt BBB function, making it more permeable and potentially allowing harmful substances from the blood to enter the brain and affect its function. Keeping the BBB strong is important for the brain and nervous system to work properly.

In an experiment with animals affected by temporal lobe epilepsy, stem cells from dental pulp and bone marrow were able to cross the brain's protective barrier when given through the bloodstream after a seizure, helping brain cells go where needed and reducing brain damage, swelling, and related problems.

When stem cells are put into a patient's body, they go into the blood and go through several steps to reach their target. First, they slow down and stick to the inside walls of blood vessels. Then they follow chemical signals from specific proteins that lead them to the right place.

It is thought that MSCs interact with endothelial cells in a multistep cascade resembling leukocytes. CXCR4 or CXCR7 ligands expressed by MSCs bind with integrin receptors including VLA-4, activated in response to chemokine receptors like stromal cell–derived factor-1 (SDF-1). When VLA-4 on MSCs interacts with VCAM-1 on endothelial cells, MSCs can stick firmly to the endothelial wall.

Once close to the injured region, stem cells transmigrate — squeezing through the walls of blood vessels — with the help of matrix metalloproteinases (MMPs) that break down the supportive layer beneath the endothelium, and via small protrusions called plasmic podia. Once through, they follow signals from the damaged area, like growth factors and chemokines, to begin repair.

Researchers such as Yilmaz and colleagues found that stem cells injected directly into the veins can move through the BBB and reach an area affected by stroke in a lab model. Within the first two hours after a stroke, MSCs travel through the lungs and then into the area of the brain that isn't getting enough blood, passing through the barrier that separates the blood from the brain.

Mesenchymal stem cells (MSCs) are considered useful for therapy because they are relatively easy to obtain, generally well tolerated, and studied for their potential to support repair in different parts of the brain. MSCs are researched for various conditions because of properties such as self-renewal, differentiation, anti-inflammatory action, and immunomodulation.

Can MSCs Get Stuck in the Lungs?

Research shows that after stem cells are put into the veins, they might get stuck in the lungs for a little while before eventually moving on to other parts of the body. MSC size varies depending on source (bone marrow, fat tissue, cord blood, or umbilical cord tissue), and cells sourced from within the body tend to be smaller, around 10 micrometers, making it easier for them to move through the bloodstream.

A 2009 study by Major and others found the typical width of a single mesenchymal stem cell taken from cord tissue to be about 11 micrometers — about the same size as a white blood cell. MSCs can also change shape, making it easier for them to squeeze through narrow blood vessels even when they are larger than the vessels, which helps them avoid getting stuck in the lungs and move throughout the body, including the central nervous system.

The blood-brain barrier is a complicated structure made up of tiny blood vessels, glial cells, integral membrane proteins, and cellular junctions that decide what goes into the brain (like glucose and amino acids) while keeping out harmful substances such as tumor necrosis factor and reactive oxygen species. The barrier is made of cells lining the inside surface of brain blood vessels, supported by neighbouring glial cells.

A strong BBB is important for healthy brain development, proper nerve function, and overall nervous system health. When it does not work properly, it can contribute to problems such as swelling and brain injury — which is why understanding how BBB cells work and interact with blood vessels helps researchers and doctors design better treatments for brain conditions.

Stem cells such as mesenchymal, neural, and embryonic stem cells are being studied for their potential to pass through the BBB and reach damaged areas in conditions like Multiple Sclerosis, Parkinson's disease, and Alzheimer's disease, using mechanisms that include the interstitial fluid pathway and communication with the cells lining blood vessel walls. As research continues, it may lead to improved treatment approaches for a range of neurological conditions.