Stem Cell Therapy for Traumatic Brain Injury

Stem Cell Therapy for Traumatic Brain Injury

Adult stem cells are found in muscles, skin, bone marrow and the brain. They remain undifferentiated in these tissues until stimulated to repair. In the gut or skin, stem cells are continuously at work whereas in other locations such as the brain, they act as a reserve. Stem cells are playing an increasingly important role in medicine – traumatic brain injury is one of many indications for this novel approach.

 

Approximately, 2.5 million people in the United States sustain a traumatic brain injury, some of which are sports-related and have been in the spotlight recently.  Concussions are the most common type of TBI. It causes a transient disturbance in brain function. Penetration injury occurs from bullets, shrapnel, and other objects entering the skull, and cause severe damage at the site they inflict. Contusions are bleeding that results from blows to the head. Diffuse axonal injury occurs from traumatic shearing forces occurring with rapid acceleration or deceleration, such as seen in a motor vehicle accident. During traumatic brain injury, the damage to brain tissues or disruption of blood supply leads to brain cell death. When the neurons die, they cannot regenerate, almost always leading to permanent neural damage.

 

TBI pathophysiology includes blood-brain barrier breakdown, widespread neuroinflammation, diffuse axonal injury, and subsequent neurodegeneration. Current therapies are noncurative and include oxygen therapy, noninvasive brain stimulation, task-oriented functional electrical stimulation, and behavioral therapies.

 

Stem cells are beginning to show promise in the treatment of TBI. Bone marrow-derived modified stem cells are being tested as a therapeutic option for TBI in a trial currently underway. These stem cells are being transplanted into the brain using minimally-invasive neurosurgical procedures with computer guidance to target the site of injury, with the aim to resolve and reverse specific deficits. There are two novel approaches under consideration – manipulation of endogenous neural cell response and administration of exogenous stem cell therapy. Exogenous stem cell transplantation promotes endogenous cellular proliferation and immature neural differentiation in the injured part of the brain.

Research suggests that TBI induces neurogenesis in animal models by stimulating neural stem cells into maturation and integration. This regenerative capacity of NSCs can be externally stimulated to promote neurogenesis. Post-TBI infusion of recombinant VEGF improved neurogenesis and promoted recovery and aid in survival of neurons. Imipramine has also been shown to enhance endogenous neurogenesis and lead to improved cognitive recovery.

In the realm of exogenous stem cells, a wide range of sources is available – embryonic, bone marrow, adipose tissue, etc. Treatment of TBI using adult stem cell transplantation is a growing field of research. Early studies have all shown that stem cell therapy enhances recovery of motor function and improved cognitive function. More recent research studies are suggesting that incorporating the use of enriched environments in stem cell can improve TBI recovery even further. Induced pluripotent stem cells (iPSCs) have also been used for TBI recovery and have shown significant recovery and maybe even preferable to embryonic stem cells.

 

Mesenchymal stem cells (MSC) are multipotent stromal cells derived from a variety of tissues [and have the capacity to differentiate into mesenchymal and nonmesenchymal tissue, including neural cells (neuron and glial-like cells). They also increase in proliferation and differentiation of native neural stem cells through chemokines and growth factors. MSCs have been shown to selectively migrate to injured tissues in TBI brain models and induce repair locally. They also have immunomodulatory properties that speed up healing.

They easily cross the BBB through paracellular pathways and the endothelial cell layers of injured tissue and therefore can be administered intravenously.

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