Traumatic brain injury (TBI) & chronic traumatic encephalopathy (CTE)

Boulder Biologics’ stem cell therapy procedures use patients’ own mesenchymal stem cells to support the recovery of traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE).

TBI / cte Issues That Stem Cells May Address

Scientists are still working to understand how to treat TBI and CTE fully. Recent evidence asserts that stem cell therapy may be a successful treatment option for the condition (1).

The stem cells’ ability to address the brain damage and excess inflammation characteristic of TBI and CTE may make them valuable in overcoming the condition (1). Read on to find out how they do so.

ABOUT STEM CELLS

Mesenchymal stem cells are able to:

  • Turn into (differentiate into) other types of cells, including (2, 3, 4):

    • Neural cells (including types of brain cells, like astrocytes)

    • Vasculature cells

    • Heart cells (including cardiac myocytes)

    • Endothelial cells of organs

    • Hepatocytes (liver cells)

    • Tendon, cartilage, bone, and muscle cells

    • Hematopoietic-supporting bone marrow cells

  • Regulate the immune system (2)

  • Promote the repair of damaged tissue (2)

STEM CELLS AND brain tissue DAMAGE

Mesenchymal stem cells are valuable to brain injury repair because they are thought to either replace damaged cells, encourage other progenitor cells to differentiate into neural cells, or call on the immune system to repair the damaged cells (1, 5).

They also may prevent further damage (as seen in CTE) by:

  • Promoting angiogenesis (the growth of new vasculature in the brain) (1, 5)

  • Preventing apoptosis (cell death) in the brain (1, 5)

  • Releasing neurotrophic growth factors (hormones that encourage tissue growth) (1, 6)

    • Including BDNF and GDNF

This process may improve brain functionality and alleviate symptoms such as reduced cognition, motor function, and memory (1 - 6).

STEM CELLS AND immune system regulation

Mesenchymal stem cells are thought to regulate the over-activated inflammatory responses associated with TBI/CTE (1, 7, 8).

Some trials have shown that mesenchymal stem cells are able to reduce inflammatory cytokine levels and interleukins, such as IL-1B and TNF-a cells, in TBI patients (1).  This immune system regulation is thought to encourage the regeneration of damaged brain tissue and discourage the development of CTE (1).

What is Autologous Bone Marrow-Derived Mesenchymal STEM CELL (BM-MSC) therapy?

BM-MSC therapy supplies the body with a high concentration of mesenchymal stem cells derived from the patient’s own bone marrow. These cells augment damaged tissue’s ability to rebuild and recover and may regulate the immune system.

The procedure first involves aspirating bone marrow from the patient’s PSIS, which is located in the posterior pelvis area. The bone marrow aspirate (BMA) is filtered and can be used en masse or by concentrating the BM-MSCs using density gradient centrifugation.

The cells are typically administered to the patient intravenously (through an IV) and/or intranasally (through the nose). An IV is inserted into the patient’s arm, and cells may be atomized into the patient’s nasal passages. The patient lies on their back, tilted backward, for about an hour until cell delivery is complete.

Intranasal delivery is thought to increase the cells’ access to the brain, which is valuable for treating neurological issues (9).

Results and safety

Stem cells derived from a donor are called allogeneic stem cells. Those from the patient’s own body are called autologous stem cells.

Therapies that use autologous stem cells (the patient’s own cells) are traditionally much safer than those that use cells from donors. The risk of rejection is mitigated using autologous, which may be of concern with allogeneic stem cell therapy. At Boulder Biologics, we use autologous stem cells only.

Though stem cell therapy is not always effective for TBI/CTE patients, the risk of experiencing harm or adverse effects due to the procedure is extremely low. We are still collecting data and intend to emphasize that this is a novel treatment with minimal risks. 

Our preliminary clinical evidence shows that our stem cell therapy has been effective for some of our TBI/CTE patients. Those who benefitted saw improvements in memory and cognition. Not every patient experienced benefits from the treatment, but none of them experienced adverse effects.

References

  1. Schepici G, Silvestro S, Bramanti P, Mazzon E. Traumatic Brain Injury and Stem Cells: An Overview of Clinical Trials, the Current Treatments, and Future Therapeutic Approaches. Medicina (Kaunas). 2020;56(3):137. Published 2020 Mar 19. doi:10.3390/medicina56030137 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143935/ 

  2. Mesenchymal Stem Cell. Mesenchymal Stem Cell - an Overview | ScienceDirect Topics, https://www.sciencedirect.com/topics/engineering/mesenchymal-stem-cell. 

  3. Wislet-Gendebien S, Laudet E, Neirinckx V, Rogister B. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders? J Biomed Biotechnol. 2012;2012:601560. doi: 10.1155/2012/601560. Epub 2012 Jan 26. PMID: 22319243; PMCID: PMC3273046. https://pubmed.ncbi.nlm.nih.gov/22319243/ 

  4. Sekiya I, Larson BL, Smith JR, Pochampally R, Cui JG, Prockop DJ. Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem Cells. 2002;20(6):530-41. doi: 10.1634/stemcells.20-6-530. PMID: 12456961. https://pubmed.ncbi.nlm.nih.gov/12456961/ 

  5. Mahmood A, Lu D, Qu C, Goussev A, Chopp M. Human marrow stromal cell treatment provides long-lasting benefit after traumatic brain injury in rats. Neurosurgery. 2005 Nov;57(5):1026-31; discussion 1026-31. doi: 10.1227/01.neu.0000181369.76323.50. PMID: 16284572; PMCID: PMC1570382. https://pubmed.ncbi.nlm.nih.gov/16284572/ 

  6. Mahmood A, Lu D, Chopp M. Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury. J Neurotrauma. 2004 Jan;21(1):33-9. doi: 10.1089/089771504772695922. PMID: 14987463. https://pubmed.ncbi.nlm.nih.gov/14987463/ 

  7. McKee CA, Lukens JR. Emerging Roles for the Immune System in Traumatic Brain Injury. Front Immunol. 2016 Dec 5;7:556. doi: 10.3389/fimmu.2016.00556. PMID: 27994591; PMCID: PMC5137185. https://pubmed.ncbi.nlm.nih.gov/27994591/ 

  8. Hasan A, Deeb G, Rahal R, Atwi K, Mondello S, Marei HE, Gali A, Sleiman E. Mesenchymal Stem Cells in the Treatment of Traumatic Brain Injury. Front Neurol. 2017 Feb 20;8:28. doi: 10.3389/fneur.2017.00028. PMID: 28265255; PMCID: PMC5316525. https://pubmed.ncbi.nlm.nih.gov/28265255/ 

  9. Galeano C, Qiu Z, Mishra A, et al. The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System. Cell Transplant. 2018;27(3):501-514. doi:10.1177/0963689718754561 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038044/