Traumatic Brain Injury (TBI) and Chronic Traumatic Encephalopathy (CTE)

Boulder Biologics offers investigational autologous biologic procedures for selected individuals with a history of traumatic brain injury (TBI) and persistent post-traumatic symptoms. These procedures are also explored in patients with symptom patterns consistent with chronic traumatic encephalopathy (CTE), recognizing that CTE is a neuropathological diagnosis that cannot be definitively confirmed during life.

No stem cell or cellular therapy is approved by the U.S. Food and Drug Administration (FDA) for the treatment of TBI, CTE, or post-traumatic neurodegeneration. The approaches described on this page are experimental, based on evolving scientific evidence, and offered only after a comprehensive informed consent process, consistent with our approach to Long COVID and intranasal biologic therapies.

Shared Biological Features of TBI, CTE, and Post-Viral Neurocognitive Syndromes

As with Long COVID, chronic symptoms following TBI and repetitive head injury are increasingly understood to arise from secondary injury mechanisms, rather than from the initial mechanical insult alone. (1,7)

Common biological features include:

1. Persistent Neuroinflammation: Sustained activation of microglia, astrocytes, and peripheral immune signaling pathways contributes to ongoing neuronal stress and dysfunction long after the initial injury. This immune dysregulation parallels inflammatory mechanisms described in Long COVID-associated cognitive impairment. (7,8)

2. Neurovascular and Blood–Brain Barrier (BBB) Dysfunction: Disruption of the BBB and cerebral microvasculature impairs nutrient delivery, waste clearance, and neurovascular coupling mechanisms now recognized in both post-traumatic and post-infectious neurological syndromes. (2,5,6)

3. Progressive or Cumulative Injury: In individuals with repetitive head impacts, chronic inflammation, axonal injury, and abnormal protein accumulation may drive progressive cognitive, behavioral, and motor symptoms over time. (1,7)

About Mesenchymal Stromal Cell–Containing Autologous Biologics

Mesenchymal stromal cells (MSCs) are non-hematopoietic cells present in bone marrow and other tissues. Consistent with FDA-aligned scientific consensus, their primary in vivo activity is paracrine and immunomodulatory, not direct neuronal differentiation or replacement of brain tissue. (2,3,8)

As with our Long COVID program, we emphasize that any potential benefit arises from:

  • Immune modulation rather than immune suppression

  • Support of endogenous repair environments, not cell replacement

  • Neurovascular and glial signaling effects, not regeneration of lost neurons

Claims of routine differentiation into functional brain cells are not supported in human clinical data and are intentionally avoided.

Rationale for Autologous Biologic Use in Post-Traumatic Neurological Syndromes

Immune System Modulation: Preclinical and early clinical studies suggest MSC-associated biologics may reduce pro-inflammatory cytokines and influence immune cell behavior after TBI, similar to mechanisms hypothesized in Long COVID. (6-8)

Neurovascular and Tissue-Support Signaling: Animal models demonstrate increased expression of growth factors involved in angiogenesis and neurovascular support following administration of marrow-derived stromal cells. These effects are thought to improve the biologic environment for recovery, rather than replacing damaged neurons. (5,6)

Limiting Secondary Injury Cascades: By influencing inflammation, apoptosis pathways, and microvascular integrity, MSC-associated signaling may help limit secondary injury processes that contribute to chronic dysfunction and neurodegeneration. (1,5,6)

Autologous Bone Marrow–Derived Biologic Procedure (Investigational)

This investigational approach mirrors the framework used in our Long COVID program and involves:

  1. Bone marrow aspiration from the posterior superior iliac spine (PSIS)

  2. Filtration and minimal processing of bone marrow aspirate

  3. Optional concentration of cellular components

  4. Autologous administration, which may include:

    • Intravenous (IV) delivery

    • Intranasal delivery in selected cases

No donor cells, culture expansion, genetic modification, or manufactured cellular products are used.

Intranasal Delivery: Consistent CNS Access Strategy

As with Long COVID-associated cognitive dysfunction, intranasal delivery is explored as a route to allow biologic signaling molecules to access the central nervous system via olfactory and trigeminal pathways, bypassing systemic circulation. (9)

Important alignment points:

  • Intranasal delivery is investigational

  • It is not FDA-approved for neurological disease treatment

  • It is discussed as a potential access route, not a proven therapeutic pathway

Safety, Limitations, and Evidence Gaps

Consistent with our Long COVID disclosures:

  • Autologous biologics reduce immune rejection risks seen with donor-derived products

  • Published studies suggest acceptable short-term safety, but long-term efficacy is unknown (1,5-8)

  • Not all patients improve; response cannot be predicted

At Boulder Biologics:

  • Only autologous material is used

  • Patients are screened carefully

  • Treatment is framed as experimental supportive care, not disease-modifying therapy

Clinical Outcomes: Current State of Evidence

Evidence for MSC-based biologics in TBI and suspected CTE is preliminary and largely derived from:

  • Animal models

  • Small human studies

  • Early-phase clinical investigations

Reported improvements in some patients include:

  • Memory and attention

  • Cognitive endurance

  • Neurofatigue and autonomic symptoms

However:

  • Results are inconsistent

  • Controlled trials specific to CTE are lacking

  • No therapy is proven to prevent, halt, or reverse CTE

FDA Regulatory Disclosure

  • No stem cell or cellular therapy is FDA-approved for TBI, CTE, or Long COVID

  • The procedures described are investigational

  • No claims are made regarding cure, neuroregeneration, or disease modification

  • Outcomes vary; no benefit is guaranteed

This page aligns with FDA guidance on regenerative medicine marketing and avoids unsubstantiated claims.

References

1.     Schepici G, Silvestro S, Bramanti P, Mazzon E. Traumatic brain injury and stem cells: an overview of clinical trials and future therapeutic approaches. Medicina (Kaunas). 2020;56(3):137.

2.     Greene C, Connolly R, Brennan D, et al. Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment. Nat Neurosci. 2024;27:421–432.

3.     Wislet-Gendebien S, Laudet E, Neirinckx V, Rogister B. Adult bone marrow stem cells for neurodegenerative disorders. J Biomed Biotechnol. 2012;2012:601560.

4.     Sekiya I, Larson BL, Smith JR, et al. Expansion of human adult stem cells from bone marrow stroma. Stem Cells. 2002;20(6):530–541.

5.     Mahmood A, Lu D, Qu C, et al. Human marrow stromal cell treatment provides long-lasting benefit after TBI in rats. Neurosurgery. 2005;57(5):1026–1031.

6.     Mahmood A, Lu D, Chopp M. IV administration of marrow stromal cells increases growth factor expression after TBI. J Neurotrauma. 2004;21(1):33–39.

7.     McKee CA, Lukens JR. Emerging roles for the immune system in traumatic brain injury. Front Immunol. 2016;7:556.

8.     Hasan A, Deeb G, Rahal R, et al. Mesenchymal stem cells in the treatment of traumatic brain injury. Front Neurol. 2017;8:28.

9.     Galeano C, Qiu Z, Mishra A, et al. The route by which intranasally delivered stem cells enter the CNS. Cell Transplant. 2018;27(3):501–514.