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Lung disease attracted serious cell therapy research during the pandemic, and most of it studied people in intensive care. Stem cell therapy for chronic lung conditions borrows that evidence, and the borrowing does not hold: acute lung injury and chronic lung disease are different problems with different biology.
Where the trials actually are
Acute respiratory distress syndrome has randomised evidence — Mesenchymal stromal cell therapy for COVID-19 acute respiratory distress syndrome: a double-blind randomised controlled trial.
Vesicle preparations have been tested in respiratory failure — Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure From COVID-19: A Randomized, Placebo-Controlled Dosing Clinical Trial and Human placental mesenchymal stromal cell-derived small extracellular vesicles as a treatment for severe COVID-19: A double-blind randomized controlled clinical trial.
A review has summarised the pandemic-era research effort — Association between Mesenchymal Stem Cells and COVID-19 Therapy: Systematic Review and Current Trends.
Every one of those studied acutely, severely unwell patients. None studied chronic lung disease.
The neonatal evidence, and why it is different
Bronchopulmonary dysplasia in premature infants has a randomised phase II trial — Stem cells for bronchopulmonary dysplasia in preterm infants: A randomized controlled phase II trial — with five-year follow-up published — Five-year follow-up of phase II trial of stromal cells for bronchopulmonary dysplasia.
Five-year follow-up of a randomised trial is a high standard, and this is one of the better-conducted programmes in the whole field.
It is also about lungs that are still developing. A premature infant’s lung is growing, and influencing how it grows is a fundamentally different proposition from repairing an adult lung damaged over decades.
Citing neonatal results for an adult with emphysema is not a small extrapolation. It is a different organ state entirely.
Acute versus chronic
Acute respiratory distress syndrome is overwhelming inflammation flooding the lungs over hours and days, in patients who were often previously well. Suppressing that inflammation is a coherent aim.
Chronic lung disease is structural damage accumulated over years — destroyed air sacs, scarred tissue, remodelled airways. The inflammation, where present, is a different process on a different timescale.
A treatment that helps in the first situation has no particular reason to help in the second, and the trials have not been done to find out.
COPD and pulmonary fibrosis cover the two commonest chronic conditions separately, and the picture differs for each.
Why the lungs look like a promising target
Most intravenously infused cells lodge in the lungs on first pass, because the lung capillary bed is the first small-vessel network the blood reaches.
That is usually described as a limitation for treating other organs. For lung disease it is presented as an advantage, and the logic is not unreasonable.
What it does not establish is that cells arriving in a lung do anything useful there. Arriving and acting are separate questions, and only the first has been demonstrated.
Mesenchymal stem cell therapy covers what is known about cell distribution.
Nebulised delivery
Some products are offered as an inhaled mist rather than an infusion, on the reasoning that this puts material directly where it is wanted.
A clinical investigation has examined nebulised cord-derived vesicles in pulmonary fibrosis — Clinical investigation on nebulized human umbilical cord MSC-derived extracellular vesicles for pulmonary fibrosis treatment.
Nebulising a biological product into damaged lungs is not risk-free. Bronchospasm, worsening oxygenation and infection are all plausible, and none of that is addressed by describing it as natural.
Ask what is being nebulised, how it was prepared and tested, and what monitoring is in place during administration.
The conditions grouped under this heading
Asthma, bronchiectasis, interstitial lung disease, sarcoidosis, cystic fibrosis and occupational lung disease are all distinct, with distinct treatments and different outlooks.
Several have transformed in the last decade. Cystic fibrosis in particular now has modulator drugs that changed the disease for most patients, and severe asthma has multiple effective biologic options.
Grouping them as chronic lung conditions serves the seller rather than the patient. The right question is always what the specific diagnosis is and what exists for it.
If the answer is a general infusion for all of them, that is a sign the diagnosis is not driving the treatment.
The oxygen question
Oxygen saturation measured on a fingertip at rest is the number patients are most often shown, and it is the least sensitive measure available in chronic lung disease.
Saturation stays normal until quite late, then falls on exertion before it falls at rest. Someone can have substantially impaired lungs and a perfectly normal resting reading.
That makes it easy to present a reassuring figure before and after a treatment. A walk test with saturation monitored during exertion says considerably more, and takes six minutes.
If oxygen numbers are being used as evidence of improvement, ask whether they were taken at rest or during exercise.
Risks
Infusion reactions and transient fever. In patients with limited respiratory reserve, a fever and increased oxygen demand are less easily tolerated than in others.
Fluid loading during infusion matters in patients with borderline cardiac or respiratory function.
Nebulised delivery adds airway-specific risks, as above.
Travel risks for people with significant lung disease, including in-flight oxygen requirements. Documented adverse events covers the wider picture.
Questions worth asking
- What exactly is my diagnosis, and what trial exists for that specific condition?
- Is the evidence being quoted from acute respiratory failure or from chronic disease?
- Will lung function be measured before and after?
- Am I fit to fly, and do I need in-flight oxygen?
The limits of current evidence covers this pattern across the field.
Frequently asked questions
There were many lung trials during the pandemic. Do they apply to me?
Only if you have acute respiratory failure. They studied intensive care patients, not people with chronic lung disease.
What about the infant trials?
They are well conducted, with five-year follow-up, and they are about lungs that are still developing. That is a different situation from an adult lung damaged over decades.
Do cells reach the lungs?
Most infused cells do lodge there on first pass. Arriving and doing something useful are separate questions, and only the first is established.
Is nebulised treatment safer?
Not automatically. Nebulising a biological product into damaged lungs carries airway risks that should be discussed rather than assumed away.
My condition is not listed. Does that mean anything?
It usually means a literature search returned nothing specific worth describing for it.
Can lung scarring be reversed?
No published trial in adults reports that. Structural damage accumulated over years is not addressed by anything currently available.
Requesting a medical evaluation
Nothing on this page establishes whether any treatment is appropriate for you. That needs your history, your imaging and your current medications read by a clinician. If you would like that review, send your records and we will tell you honestly whether there is anything worth discussing — including when the answer is no.
This page is general information, not medical advice, and does not create a doctor–patient relationship. Regenerative treatments discussed here are in most cases investigational. Discuss any treatment with a clinician who knows your history.