The blood brain barrier (BBB) is an important part of the brain that helps to prevent the entry of unwanted substances into the brain. You can also say it is a gatekeeper of the brain.
With the help of the ongoing studies, researchers reveal that some cells such as stem cells can easily pass through this barrier. This capability of stem cells opens various new pathways to treat brain disorders.
In this article, we will provide you brief information about the challenges of the blood brain barrier, how it can protect the brain, and the potential of stem cells to cross this barrier to provide exceptional treatments for neurological treatments.
Crossing of Mesenchymal Stem Cells Through 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. It has been confirmed in the research that includes a study by Kim and the research says that if MSCs are injected through a vein, then it can easily pass through the BBB. This was proven in a mouse model for Alzheimer’s Disease, showing their potential to help regenerate brain tissue.
Important Features of MSCs
- Anti-Inflammation: These cells find the inflamed area and migrate through it naturally.
- Release of Secretomes: They release compounds that help relieve pain and regenerate nerves.
- BBB Crossing Capabilities: MSCs can traverse the blood-brain barrier when administered intravenously.
What is the Blood Brain Barrier?
The important protective layer around the brain and spinal cord is known as the blood brain barrier. With the help of this shield, it is not easy for harmful substances to enter the brain. These cells are called brain endothelial cells. They cover the blood vessels in the brain. They stick tightly to each other through special connections called junctional adhesion molecules. This makes a strong barrier.
Components and Function of the BBB
- Brain Endothelial Cells: BBB’s primary structure is formed by these cells.
- Tight Junctions: it ensures a strong barrier between cells.
- Selectively Permeability: Control the entry and exit of the substances.
What is the Impact of BBB on Stem Cell Therapy?
The blood brain barrier is made up of several complex networks of blood vessels and cells. It is a critical structure of the brain and controls the entry and exit of the substances between bloodstream and central nervous system (CNS) like a protective shield.
This barrier is really important for keeping the brain balanced and helps stem cell treatments for brain problems work better.
Factors Affecting the Delivery of Stem Cells Through the BBB
- Extracellular Vesicles: Extracellular vesicles are derived from mesenchymal stem cells such as exosomes that can travel from the barrier. These vesicles can be administered through intravenous or intranasal without the need of the surgery.
- Function of Barrier: The BBB can stop some special cells from going into the brain, which can change how helpful they are for treatments. A study found that stem cells from human skin injected soon after a temporary lack of blood flow to the entire brain couldn’t get through a damaged barrier that protects the brain.
- Administration Timing: Stem cell therapy success is dependent when the cells are administered in relation to BBB damage. In a study on epilepsy, researchers found that giving certain types of cells at the right time after a seizure can help them find their way to the brain and reduce damage to the brain’s protective barrier. This can lessen brain cell death and other problems caused by epilepsy.
Additional Research Information
Scientists are finding out that special cells called mesenchymal stem cells can go through a barrier in our body called the blood-brain barrier. This discovery could lead to new ways of treating brain problems.
In an experiment with animals that had epilepsy affecting the temporal lobe, stem cells from dental pulp and bone marrow were able to get through the brain’s protective barrier when given through the bloodstream after a seizure.
This helped brain cells go where they needed to, and it made problems like brain damage, brain swelling, and mental health issues not as bad.
Interactions
- Deliver through Intravenous and Intranasal: MSCs contain exosomes like extracellular vesicles which have the potential to cross the BBB. Delivery through intravenous or intranasal routes can provide the therapeutic benefit and neglect the use of neurosurgery.
- TLE Model Experiment: Giving certain types of cells at specific times helped improve brain problems in TLE.
- Role of MSCs in Neurological Treatment: They have the potential to treat different neurological conditions.
The Regulation of Nutrients by Brain Capillary Endothelial Cells
Brain capillary cells are like gatekeepers for the brain. They make sure the brain gets what it needs to stay healthy, like food (glucose) and building blocks (amino acids), while blocking out harmful stuff. They also control how much blood goes to your brain, which is important because your brain needs oxygen and food to work well.
BBB Formation and Vascular Endothelial Growth Factor
The BBB needs something called vascular endothelial growth factor (VEGF) to form and work properly. This protein helps build and keep the cells lining the tiny blood vessels in the brain. These cells are important for the BBB’s barrier. The BBB stops a lot of immune cells, such as white blood cells and T cells, from going into the brain. This helps keep the brain safe from swelling and harm.
Weak Points and Circumventricular Organs in the BBB
Circumventricular organs are the areas of the brain where the blood brain barrier is weaker than other areas and some substances can come inside easily. Some things that dissolve in fat can go through the BBB. But things like essential amino acids need special systems to get through.
Cerebrospinal Fluid Barrier
The cerebrospinal fluid (CSF) is important for the BBB too. It’s like a cushion around the brain and spinal cord, keeping them safe and helping to clean up waste. The cerebrospinal fluid barrier is made by special cells that cover the inside of the brain’s chambers. These cells keep the fluid in the brain separate from the blood flowing through the body.
Effects on Brain Health by Disruption in BBB Function
Sometimes, things like brain tumors or strokes can mess up how the BBB works. This can make the BBB permeable. This can potentially harm the brain cells and affect the functioning of the brain by allowing the substances from the blood to enter the brain. Keeping the BBB strong is super important for your brain and nervous system to work right.
Stem Cell Therapy for Neurodegenerative Diseases
Stem cells have the potential to treat neurodegenerative diseases. There are several stem cells such as mesenchymal, neural, and embryonic stem cells that can pass through the blood brain barrier (BBB) and reach their target. These cells provide remarkable results and become the best approach in cellular therapy for neurodegenerative diseases.
The blood brain barrier stops harmful substances from entering the brain. However, stem cells can get past this barrier. When the brain is injured or has a disease, the BBB becomes weaker, allowing stem cells to pass through and reach the damaged area. Even though the blood-brain barrier is selective, stem cells can move through the cells lining the blood vessels in two ways: between the cells or through the cells. They then go to the area of inflammation or injury in the brain to help with healing. In injuries to the central nervous system like traumatic brain injury, stroke, brain tumor, or aging, the connections between cells become weaker. This creates small gaps between the cells, allowing other cells to move through these spaces.MSCs have also been reported to break apart and separate tight connections between endothelial cells.
MSCs’ Systemic Homing Process
When stem cells are put into a patient’s body, they go into the blood and go through several steps to get to 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 that resembles leukocytes, which leads to their systemic homing. When doctors use MSCs for treatment, the cells first go into the blood. The homing process starts when MSCs slow down and touch the endothelial wall. They do this by sticking to selections on the endothelial cells. Then, they begin to move along the blood vessel wall. CXCR4 or CXCR7 ligands expressed by MSCs bind with integrin receptors including VLA-4 are activated in response to G-protein-coupled chemokine receptors like stromal cell-extracted factor-1 (SDF-1). After integrin activation, MSCs stop moving and stick to the endothelial membrane. This happens because certain integrins, such as VLA-4 found on MSCs, connect with VCAM-1 on endothelial cells. Activation one time makes integrins, which are important for cells stopping, more likely to stick together. So, when VLA-4 and VCAM-1 interact, MSCs can stick firmly to endothelial cells.
Stem cells must leave blood arteries and enter brain tissue as soon as they are close to the injured region of the brain. This is done by the process called transmigration in which they squeeze through the walls of the blood vessels. Once they leave the blood vessels, the stem cells follow more chemical signals to find exactly where they’re needed. They start their work of repairing the damaged cells once they reach the right place.
After that, MSCs move through the thin layer of cells on the inner surface of blood vessels and the supportive layer underneath, with the help of certain substances called matrix metalloproteinases (MMPs). These substances break down the supportive layer, making it easier for the MSCs to pass through. Breaking apart and dividing the connections between endothelial cells could make it easier for MSCs to move through them. MSCs have also been said to enter the endothelial layer through small protrusions called plasmic podia. In the end, MSCs move to the place where there’s an injury. They follow signals from the damaged area, like growth factors and chemokines.
Explaining Animal Stroke Model for crossing the BBB by Stem Cells
Mesenchymal stem cells can help fix problems in the brain and spinal cord caused by diseases like Multiple Sclerosis, Parkinson’s disease, and Alzheimer’s disease. Yilmaz and colleagues discovered that when you inject certain stem cells directly into the veins, those cells can move through the barrier that protects the brain and reach an area affected by stroke in a lab model. Scientists checked if MSCs (a type of cell) can move into the brain by using a special camera to see where radioactive MSCs went after they were given to rats. Within the first two hours after a stroke, special cells called MSCs travel through the lungs and then move into the area of the brain that isn’t getting enough blood. They’re able to pass through the barrier that separates the blood from the brain. The research found that when mesenchymal stem cells (MSCs) were given through a vein, they could travel to the central nervous system (CNS) after crossing the blood-brain barrier (BBB).
What Is the Unique Quality of Mesenchymal Stem Cells (MSCs)?
Mesenchymal stem cells (MSCs) are great for therapy because they are easy to get, known to be safe, and could help fix different parts of the brain. MSCs are often used to treat different diseases because of their properties such as self-renewable, differentiation, anti-inflammatory,and immunomodulatory. Research done in a lab and inside living beings has helped researchers learn more about how MSC therapy works, whether it’s safe, and if it’s effective for medical treatments.
Can MSCs Get Stuck in the Lungs?
Research shows that after you put stem cells into your veins, they might get stuck in your lungs for a little while, but eventually, they move on to other parts of your body. Cells can get stuck in some places because they’re too big. Mesenchymal stem cells (MSCs) come in different sizes depending on where they come from, like bone marrow, fat tissue, cord blood, or umbilical cord tissue. Basically, the MSCs that come from within your body are smaller, around 10 micrometers. This makes it easier for them to move around your body through your bloodstream.
In a study from 2009 by Major and others, they found that the typical width of a single mesenchymal stem cell taken from cord tissue is about 11 micrometers, which is about the same size as a white blood cell. Mesenchymal stem cells can change shape, making it easier for them to squeeze through narrow blood vessels, even when they are bigger than the vessels. This information shows that MSCs can avoid getting stuck in the lungs and can move easily throughout the whole body, including the central nervous system.
What Are the Importance of the BBB in Brain Health?
The blood-brain barrier is really important in your brain. It keeps bad stuff out and helps keep your brain healthy. It is a complicated organ full of tiny blood vessels, glial cells, integral membrane proteins, and cellular junctions that decide what goes into the brain, like food, and keeps out bad stuff.
The BBB makes sure only tiny molecules and important stuff like fatty acids can get into the brain. Bad things like tumor necrosis factor and reactive oxygen species are kept away. The barrier is made of cells that line the inside surface of blood vessels in the brain. These cells are supported by neighboring cells like glial cells.
A strong BBB is really important for your brain to grow well, for nerves to work right, and to keep your nervous system healthy. When the BBB will not work properly, it can cause problems like swelling and harm to the brain. So, it is really important to know how the cells in the BBB work and how they can interact with the blood vessels. This helps doctors to make treatments for brain problems.
Studying the BBB has taught us a lot about keeping our brains healthy. We can learn even more by looking at animal brains and seeing how the pineal gland helps control our heart health. Keeping the blood-brain barrier strong helps the brain work well and stay healthy.
The Potential of Stem Cells to Pass Through the Blood-Brain Barrier
Stem cells are those innovative cells that can pass through the blood brain barrier (BBB) and treat many neurological disorders effectively. On the other hand, BBB stops the path of most various substances which can be harmful for the brain, but stem cells have potential to penetrate the barrier.
There are several mechanisms used to bypass the barrier and one of them involves the interstitial fluid. Also, stem cells can talk to the lining of the BBB and the cells on blood vessel walls. This helps them get into the brain tissue.
Sometimes, stem cells can use problems with the BBB. This can happen when someone has certain brain problems or injuries. This helps stem cells move into the affected parts of the brain and do their job to make things better. Scientists have learned a lot about how stem cells move through the BBB by doing research. They’ve published studies about it in important science journals, like Cold Spring Harbor Perspectives.
As we learn more, we can make better treatments using stem cells to help with brain problems. This can make people’s brains healthier and make their lives better.
