Hyperbaric oxygen therapy is a medical treatment that delivers 100 percent oxygen at 2.0 to 2.4 atmospheres of pressure inside a sealed chamber. One of its most useful and least talked-about effects is that each session releases a wave of stem cells from bone marrow into the bloodstream, where they then travel to injured tissue and help rebuild it.
TL;DR: Each HBOT session roughly doubles the number of bone-marrow progenitor cells circulating in the bloodstream, and a course of 20 sessions can produce an eight-fold increase. These cells are not the kind found in stem-cell injection clinics; they are your own endothelial progenitor cells, summoned out of bone marrow by the brief drop in oxygen that follows leaving the chamber. Once in circulation, they home to ischaemic and irradiated tissue and contribute directly to new blood vessel formation. This mechanism is part of why HBOT works for delayed radiation injury, diabetic wounds, and several other Health Canada-recognised conditions treated at the 11 hospital hyperbaric programmes across Canada.
What kind of stem cells are we talking about?
The term “stem cell” gets used loosely. To avoid confusion, here is the precise category that HBOT mobilises.
The cells released by HBOT are endothelial progenitor cells (EPCs), identified in laboratory work by the surface marker CD34. Some studies also count CD45-dim cells and other vasculogenic-progenitor populations. These are not embryonic stem cells. They are not the pluripotent cells that can become any tissue type. They are also not the mesenchymal stem cells that some private clinics market as “stem cell therapy” injections (often derived from adipose tissue or umbilical cord blood and not approved by Health Canada for therapeutic use).
Endothelial progenitor cells are tissue-restricted. Their job in the body is to repair and grow blood vessels. They live in bone marrow under normal conditions, releasing into circulation in small numbers daily. They flood out in larger numbers in response to injury, exercise, ischaemia, and certain medications. Hyperbaric oxygen is one of the few non-pharmacological interventions documented to mobilise them reliably and reproducibly.
This distinction matters because patients sometimes ask whether they should combine HBOT with stem cell injection therapy at a private clinic. The answer for Health Canada-recognised indications is almost always no: HBOT mobilises your own progenitor cells from bone marrow, where they are already calibrated to your immune system, free of contamination, and not subject to the regulatory and clinical concerns surrounding unlicensed cellular products. Combining HBOT with unapproved stem cell injection at the same time can introduce safety questions for which there is no evidence base.
How does HBOT mobilise these cells?
The mobilisation pathway was worked out in a series of human studies by Stephen Thom and colleagues at the University of Pennsylvania starting in the mid-2000s. The mechanism has three stages.
Stage one: oxygen-induced nitric oxide signalling. The high oxygen tensions during a hyperbaric session activate endothelial nitric-oxide synthase (eNOS) in vascular tissue. Nitric oxide stabilises hypoxia-inducible factor 1 alpha (HIF-1α) within bone-marrow stromal cells, even at normal oxygen levels, by interfering with the prolyl-hydroxylases that normally degrade it.
Stage two: matrix metalloproteinase activation. The stabilised HIF-1α drives transcription of matrix metalloproteinase 9 (MMP-9), which cleaves the molecular tether (KIT-ligand binding to KIT receptor) that holds progenitor cells in their bone-marrow niche. With the tether cleaved, the cells are free to enter circulation.
Stage three: chemokine-directed homing. Once in the bloodstream, the progenitor cells use the CXCR4 receptor to follow stromal cell-derived factor 1 (SDF-1) gradients. SDF-1 is upregulated in ischaemic and irradiated tissue. The progenitor cells home to those gradients, embed in the local endothelium, and contribute directly to new vessel formation. This is a continuous link between Sunday’s blog post on angiogenesis and today’s: the new vessels grown in irradiated tissue are partly built from cells released by the very same hyperbaric sessions.
How many stem cells does a course of HBOT actually release?
The numbers are striking and well documented.
- One session, 120 minutes (2 hours) at 2.0 ATA: roughly doubles the circulating CD34-positive progenitor cell population (Thom 2006).
- 20 sessions over four weeks: approximately eight-fold increase from baseline (Thom 2006, replicated in subsequent series).
- 40 to 60 sessions (the typical Marx-protocol radiation injury course): sustained elevated mobilisation throughout the course, with a return toward baseline a few weeks after the final session.
For comparison, the pharmacological gold standard for stem cell mobilisation in haematology is granulocyte colony-stimulating factor (G-CSF), used to harvest stem cells before bone marrow transplantation. G-CSF achieves higher absolute counts but does so at the cost of bone pain, splenomegaly risk, and short-term immune effects. HBOT achieves a smaller but clinically meaningful mobilisation with no pharmacological burden, which is part of why it is well tolerated by older patients, cancer survivors, and people with multiple comorbidities.
Where do the mobilised cells go, and what do they do?
The progenitor cells released by HBOT do not circulate aimlessly. They home to ischaemic and damaged tissue using gradient signals.
- Irradiated tissue: radiation injury upregulates SDF-1 expression in damaged microvasculature. HBOT-mobilised EPCs home to these regions and contribute to the angiogenesis described in the previous post in this series. This is part of why HBOT works for radiation cystitis, radiation proctitis, osteoradionecrosis, and chest-wall radionecrosis after breast cancer.
- Diabetic foot wounds: Thom and colleagues showed in 2011 that HBOT increased EPC counts at the wound margin in diabetic patients with refractory ulcers, consistent with the mobilisation-and-homing pathway it describes.
- Acute stroke (off-label, investigational): a 2018 study found that adjunctive HBOT after acute non-cardioembolic stroke increased circulating EPCs and was associated with improved short-term neurological outcomes. The evidence is preliminary but biologically consistent with the mobilisation pathway.
- Cardiac ischaemia: HBOT-mobilised cells can home to ischaemic myocardium in animal studies. Human evidence remains limited and the indication is not Health Canada-recognised.
- Bone repair: mesenchymal stromal cells in bone marrow respond to HBOT with improved osteogenic and vasculogenic properties (in-vitro work confirmed in 2020), supporting the long-standing clinical use of HBOT for refractory osteomyelitis.
Why does this matter for cancer survivors specifically?
Daffodil Month is when many cancer survivors first hear about HBOT, often as a treatment option for the late effects of radiation therapy years after their cancer treatment ended. Stem cell mobilisation is part of why the treatment can be effective so long after the original radiation.
Radiation damages the small blood vessels in the treatment field, leaving tissue chronically hypoxic. Without enough oxygen, the tissue cannot repair itself. The body’s normal response to ischaemia, which is to mobilise EPCs and grow new vessels, is impaired in irradiated tissue because the local SDF-1 signalling is intact but the bone marrow’s response capacity may be compromised by age, comorbidity, or prior chemotherapy. HBOT compensates: by repeatedly mobilising progenitor cells from bone marrow and pushing them into circulation, it helps the body do what it would otherwise struggle to do on its own.
This is why a treatment course of 30 to 60 sessions can produce permanent improvement in tissue oxygenation and symptom relief that lasts long after the patient finishes treatment. The new blood vessels persist. The progenitor cells that helped build them have already done their job and gone home.
Does HBOT-mobilised stem cell activity affect cancer recurrence risk?
This is the most common patient concern, and it deserves a direct answer.
The Undersea and Hyperbaric Medical Society’s published position is that HBOT does not promote cancer recurrence in survivors with controlled or treated disease. The cells mobilised by HBOT are tissue-repair progenitors with restricted lineage; they do not have the unlimited self-renewal or multilineage differentiation properties of cancer stem cells. The angiogenesis they support is normal vascular regeneration, not tumour neovascularisation. Multiple clinical reviews of cancer survivors treated with HBOT for late radiation effects have not detected an increased recurrence rate.
That said, most hyperbaric medicine programmes confirm with the patient’s oncology team that the cancer is in remission before starting treatment. Patients with active untreated cancer in the field are typically managed differently, and the timing of HBOT relative to active treatment is decided in consultation with the oncologist.
| Indication | Mobilisation evidence | Status in Canada |
|---|---|---|
| Delayed radiation injury (cystitis, proctitis, ORN, chest-wall) | Strong: cellular + clinical evidence | Recognised; covered at 11 hospital programmes |
| Diabetic foot ulcer (refractory) | Strong: Thom 2011 cellular evidence + Cochrane clinical evidence | Recognised (problem wounds); covered at hospital programmes |
| Refractory osteomyelitis | Strong: cellular + clinical evidence (in-vitro 2020) | Recognised; covered at hospital programmes |
| Acute ischaemic stroke (adjunct) | Preliminary: 2018 study, small cohort | Investigational; not a recognised indication |
| Cardiac ischaemia | Animal-model evidence; limited human data | Not a recognised indication |
| Aging / longevity (Hachmo 2020 telomere study) | Mobilisation observed in healthy subjects | Investigational; not a recognised indication |
What is the practical takeaway for patients?
If you are considering HBOT for a Health Canada-recognised indication, the stem cell mobilisation effect is part of what you are getting. You do not need to do anything extra to receive it. The mobilisation happens automatically with each session, with no medication, injection, or harvest. You will not feel the cells releasing into circulation any more than you feel a normal hormonal response to exercise.
If you are being offered HBOT alongside paid stem cell injection therapy at a private clinic, ask carefully about the cellular product, its source, its regulatory status with Health Canada, the evidence supporting its use for your specific condition, and whether the combination has been studied. For Health Canada-recognised indications treated at a hospital programme, the standard course of HBOT alone is sufficient and the additional unapproved product adds cost without proven benefit.
How is HBOT for these indications covered in Canada?
HBOT for the 14 Health Canada-recognised conditions is covered by provincial health insurance at the 11 hospital hyperbaric programmes in Canada. These are in Ontario (Toronto General, Hamilton General, The Ottawa Hospital), Quebec (Sacré-Coeur Hospital, Hôtel-Dieu de Lévis), British Columbia (Vancouver General Hospital), Alberta (Misericordia Edmonton, Foothills/AJECCC Calgary), Nova Scotia (QEII Halifax), Newfoundland (Health Sciences Centre St. John’s), and Saskatchewan (Wigmore Hospital, Moose Jaw, capacity permitting). A physician referral is required.
Patients in provinces or territories without an in-province hospital programme (Manitoba, New Brunswick, Prince Edward Island, Yukon, Northwest Territories, Nunavut) are referred inter-provincially, most commonly to Edmonton or to one of the Ontario programmes depending on geography.
April Daffodil Month, led by the Canadian Cancer Society, is a useful reminder for survivors to ask whether late radiation effects might respond to HBOT. The verified Canadian directory at /facilities/ lists all 33 hyperbaric facilities (11 hospital programmes plus 22 private clinics across nine provinces). Canada Hyperbarics also publishes detailed condition-specific guides for each of the recognised indications, including delayed radiation injury, refractory osteomyelitis, and problem wounds.
Frequently asked questions
Are the stem cells released by HBOT the same as those used in stem cell therapy clinics?
No. HBOT mobilises your own endothelial progenitor cells from bone marrow into circulation; these are tissue-restricted cells that repair blood vessels. Stem cell therapy clinics typically inject mesenchymal stem cells from a different source (adipose tissue, umbilical cord blood) and target a different mechanism. The cellular biology, the regulatory status, the safety profile, and the evidence base are all different. For Health Canada-recognised indications, HBOT alone is the standard of care.
How many HBOT sessions before stem cell mobilisation peaks?
A single 2-hour session (120 minutes) at 2.0 ATA roughly doubles circulating progenitor cells. The increase compounds across sessions, reaching about an eight-fold increase by session 20 and remaining elevated throughout a 30 to 60 session course. The full clinical effect, in terms of new blood vessel formation and tissue repair, is typically evaluated at the end of the course rather than mid-course.
Does the stem cell effect last after I finish HBOT?
The mobilisation effect itself fades over a few weeks once treatment ends, returning to baseline circulation levels. The downstream tissue effect, meaning the new blood vessels and repaired tissue, is permanent. The cells did their job during the course; you do not need ongoing mobilisation to maintain the benefit.
Can HBOT cause cancer cells to grow back through stem cell mobilisation?
Current evidence does not support this concern. The cells mobilised by HBOT are tissue-repair progenitors, not the unlimited self-renewing cells that drive cancer. Multiple reviews of cancer survivors treated with HBOT for late radiation effects have not found an increased recurrence rate. Most hyperbaric programmes confirm with oncology that the cancer is in remission before starting treatment.
Why is HBOT not a recognised indication for stroke or heart attack in Canada?
The cellular evidence is consistent (HBOT does mobilise progenitor cells that home to ischaemic tissue), but the clinical-trial evidence in stroke and cardiac ischaemia is preliminary and small-cohort. Health Canada-recognised indications require a higher evidence threshold than HBOT currently has for these conditions. A few academic groups in Canada and internationally are studying HBOT in acute stroke, and the literature continues to grow.
Is the stem cell mobilisation effect different in older patients?
Older patients (60+) tend to have a smaller absolute increase in circulating progenitor cells per HBOT session, but the relative increase (the multiplier from baseline) is similar. The clinical response is generally also similar, suggesting that the mobilisation pathway remains functional with age. There is no upper age limit on HBOT for recognised indications.
What if I have already had a bone marrow transplant: does HBOT still mobilise stem cells?
Yes. Mobilisation is from your current bone marrow regardless of whether the cells are autologous or from a transplant. Patients with a history of haematopoietic stem cell transplant who develop hemorrhagic cystitis are routinely treated with HBOT in some programmes, and the mobilisation pathway is part of the response.
Where can I find a hospital hyperbaric programme in my province?
Canada Hyperbarics maintains a verified directory at /facilities/ with all 33 facilities including the 11 hospital programmes covered by provincial health insurance. The condition-specific page on delayed radiation injury also lists which programmes accept referrals for cancer survivorship indications.
References and further reading
- Thom SR, Bhopale VM, Velazquez OC, et al. Stem cell mobilization by hyperbaric oxygen (American Journal of Physiology Heart and Circulatory Physiology 2006).
- Thom SR, Milovanova TN, Yang M, et al. Vasculogenic stem cell mobilization and wound recruitment in diabetic patients (Wound Repair and Regeneration 2011).
- Velazquez OC. Angiogenesis and vasculogenesis: inducing the growth of new blood vessels and wound healing by stimulation of bone marrow-derived progenitor cell mobilization and homing (J Vasc Surg 2007).
- Fosen KM, Thom SR. Hyperbaric oxygen, vasculogenic stem cells, and wound healing (Antioxidants & Redox Signaling 2014).
- Chen CY, Wu RW, Tsai NW, et al. Increased circulating endothelial progenitor cells and improved short-term outcomes in acute non-cardioembolic stroke after HBOT (J Transl Med 2018).
- Hachmo Y, Hadanny A, Abu Hamed R, et al. Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. Aging (Albany NY). 2020;12(22):22445-22456.
- Health Canada. Notice on hyperbaric oxygen therapy.
- Canadian Cancer Society. Daffodil Month.
Disclaimer
This article is provided by Canada Hyperbarics for informational purposes only and is not medical advice. Do not delay or replace medical care based on what you read here. Always speak with your radiation oncologist, your family physician, and a hospital-based hyperbaric medicine specialist before starting hyperbaric oxygen therapy. Treatment courses, contraindications, and coverage details should be confirmed directly with the receiving hyperbaric programme. Canada Hyperbarics is an independent educational resource and has no commercial relationship with the hospital programmes or other organisations referenced above. Combining HBOT with unapproved cellular products at private stem cell injection clinics is not a recognised standard of care and is not recommended for the indications discussed in this article.