STEM Cell Therapy for COVID-19 Long Haulers

Stem cell therapy procedures use patients’ own mesenchymal stem cells to support the recovery of post-COVID syndrome, also known as “Long COVID.”

Long COVID Issues That Stem Cells May Address

Scientists are still working to understand the post-COVID syndrome fully. However, certain features are concretely associated with long-haulers, including (1):

  • Organ tissue damage (1)

    • Long-hauler patients often have lung or heart damage associated with shortness of breath or heart palpitations.

  • Excessive inflammation (1)

    • Long COVID patients often have hyperactive immune systems characterized by elevated cytokines like IL-6 and unusual T-cell activity. This immune system dysregulation is thought to cause neurological issues and systemic fatigue.

  • Disruption of the Blood-Brain Barrier (BBB) (2)

    • Sustained systemic inflammation and BBB dysfunction are attributed to the brain fog and cognitive impairment experienced by long COVID patients.

Stem cells’ ability to address these features of the post-COVID syndrome may make them a valuable tool in overcoming long COVID. 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 (3):

    • Heart cells (including cardiac myocytes)

    • Endothelial cells of organs

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

    • 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 ORGAN DAMAGE

Upon contracting COVID-19, organ tissue (such as lung tissue) may become damaged (1). Healing the tissue requires repairing or replacing damaged cells.

Mesenchymal stem cells are valuable to organ injury repair because they are thought to either replace damaged cells or help repair them through paracrine (cell-to-cell signaling) mechanisms (3).

This process may result in improved functionality of damaged organs and thereby alleviate symptoms such as shortness of breath and heart palpitations (4).

STEM CELLS AND immune system regulation

Mesenchymal stem cells are thought to regulate the over-activated inflammatory responses associated with Long COVID (4).

Some trials have shown that mesenchymal stem cells are able to reduce inflammatory cytokine levels, increase anti-inflammatory interleukins such as IL-10, and oust overactive T-cells and NK (natural killer) cells in COVID-19 patients (6). 

This immune system regulation is thought to alleviate neurological and fatigue-related symptoms (4).

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 (8).

We intranasally atomize the patient’s cells so that the cells can enter the brain to take action.

RESULTS AND SAFETY

Stem cells derived from the patient’s own body are called autologous stem cells. Those from a donor are called allogeneic 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, 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 long-haul patients. 

Those who saw benefits reported improved autonomic dysfunction, fatigue levels, and cognitive impairments. Not every patient experienced benefits from the treatment, but none of them experienced adverse effects.

References

  1. Post-Covid Conditions, Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html.

  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 27, 421–432 (2024). https://doi.org/10.1038/s41593-024-01576-9

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

  4. Shi, L., Wang, L., Xu, R. et al. Mesenchymal stem cell therapy for severe COVID-19. Sig Transduct Target Ther 6, 339 (2021). https://doi.org/10.1038/s41392-021-00754-6

  5. Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, Shan G, Meng F, Du D, Wang S, Fan J, Wang W, Deng L, Shi H, Li H, Hu Z, Zhang F, Gao J, Liu H, Li X, Zhao Y, Yin K, He X, Gao Z, Wang Y, Yang B, Jin R, Stambler I, Lim LW, Su H, Moskalev A, Cano A, Chakrabarti S, Min KJ, Ellison-Hughes G, Caruso C, Jin K, Zhao RC. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia, Aging Dis. 2020 Mar 9;11(2):216-228. doi: 10.14336/AD.2020.0228. PMID: 32257537; PMCID: PMC7069465. https://pubmed.ncbi.nlm.nih.gov/32257537/

  6. Song, Na, et al. Mesenchymal Stem Cell Immunomodulation: In Pursuit of Controlling COVID‐19 Related Cytokine Storm. Stem Cells (AlphaMed Press), John Wiley & Sons, Ltd, 7 Mar. 2021, https://stemcellsjournals.onlinelibrary.wiley.com/doi/10.1002/stem.3354.

  7. Beghini DG, Horita SI, Henriques-Pons A. Mesenchymal Stem Cells in the Treatment of COVID-19, a Promising Future. Cells. 2021; 10(10):2588. https://doi.org/10.3390/cells10102588

  8. 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/