December 1, 2020

The Niche

Knoepfler lab stem cell blog

On stem cells for lungs the-profit clinic offerings don’t make much sense

What’s the deal with lung stem cells and stem cells for lungs?

For a long time researchers found that stem cells were elusive in adult lungs. There was debate about whether they even existed, but it now seems fairly established that there are some of the little guys in there. Just because one of the early papers on purported human lung stem cells came from Piero Anversa and has been retracted doesn’t mean these stem cell cells don’t exist at all. Other groups have reported on their existence. Also, lung organoids can be grown from stem and progenitor cells, which is a powerful relatively new tool. You can see some lung organoids at right from recent cool research done at Penn.

"Mouse (left) and human (right) alveolar progenitor cells grow into large lung organoids in culture, and make multiple types of epithelial cells including gas exchange type 1 cells (red) and surfactant-producing type 2 cells (green). Credit: led by Edward E. Morrisey, PhD, Perleman School of Medicine, University of Pennsylvania."
“Mouse (left) and human (right) large lung organoids have multiple types of cells including type 1 (red) and type 2 pneumocytes (green). Images credit: led by Edward E. Morrisey, PhD, Perleman School of Medicine, University of Pennsylvania.” Condensed material from Penn.

However, if we flip things around and instead of asking about “lung stem cells” we ask about “stem cells for lungs” (i.e. using stem cell products to treat lung or other respiratory diseases), I’m very skeptical at this time. Unfortunately, there is a variety of unproven stem cell or related “stuff” being sold for lung disease by for-profit clinics.

One of the most well known lung and stem cell-related clinic businesses has been called The Lung Institute or now The Lung Health Institute. As far as I know they are still the subject of a proposed class action lawsuit. Note that the number of lawsuits again stem cell clinics and related firms continues to grow.

If we think about the idea of stem cell treatments for lungs, two modalities are being pitched. First, some places are claiming that IV injections of stem cells or even PRP (platelet rich plasma) help respiratory problems, while others promote what generally might be referred to as inhalation (or airway infusion) of stem cells or at least materials purported to contain stem cells. In both cases, the potential for benefit from the “stem cells” seems low-to-non-existent given that there are common sense hurdles and challenges. For instance, IV infusions aren’t likely to deliver healthy, persistent populations of stem cells to lungs and even less likely to deliver them to the rest of the respiratory tract. While it is true that there have been reports of stem cells “being filtered out” in the lungs after IV injection that doesn’t mean the cells survive or do anything helpful.

They could definitely do harm too.

The lungs are literally crawling with macrophages and it’s quite possible they view foreign stem cells (e.g. why would fat stem cells be present in lungs?) as invaders that should be eaten. This same kind of fate could await cells that are inhaled. I’m not sure it is really even known if inhaled cells would make it deep enough in the respiratory tract to get into the lungs. Higher up, they would likely get trapped in mucous and/or be coughed back out.

Despite all of this, there are loads of stem cells trials for lung diseases listed on Clinicaltrials.gov right now as of late 2018. Some are sponsored by for-profit clinics, but many others are by research institutions. Notably, some years back a placebo-controlled study of prochymal for COPD did not show benefit.

Others are skeptical too as seen in this quote from a site called PulmonaryAdvisor:

“At present, there has not been any clinical trial which has demonstrated therapeutic efficacy using stem cells to treat COPD in patients,” said Darcy E. Wagner, PhD, of the Department of Experimental Medical Sciences, Wallenberg Center for Molecular Medicine and Lund Stem Cell Centre at Lund University in Sweden, in an interview with Pulmonology Advisor. “While several different stem cell therapies have been shown to be promising in animal models of COPD, they have not been successfully translated into the clinic. There is still a general lack of understanding of potential mechanisms of action and therefore it is difficult to understand how to best translate findings in the animals into the clinic.”

I have to agree with Dr. Wagner on that.

Given the sometimes incurable, progressive nature of some lung disease and the suffering of those involved, stem cells should be explored as an option. However, in terms of actual experimental interventions in patients in my view they should only be done in rigorous placebo-controlled, true clinical trials in which patients do not have to pay.

Basic and translational research into lung stem cells and their potential use or use of other cells for respiratory diseases are important for providing real hope too. See a nice overview of this kind of research here on EuroStemCell.

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