Australian research has shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells can help regenerate damaged lung tissue in an experimental model of asthma.

The study found that the stem cells could tackle asthma on multiple levels – reducing inflammation, reversing signs of airway remodelling, and normalising airway hyperresponsiveness.

The researchers said mesenchymal stem cells may provide a novel stand-alone or adjunct therapy for people with asthma who do not respond to current therapy.

The limbic spoke to lead researcher Associate Professor Chrishan Samuel, from the Biomedicine Discovery Institute at Monash University.

What’s special about iPSC-derived mesenchymal stem cells? How can they deliver benefit across a number of asthma indicators when other stem cells have failed?

iPSCs are adult stem cells that have the ability to reproduce themselves indefinitely, proliferate, and differentiate into other cells types in the body. In this case, the iPSCs were used as starting material to generate mesenchymal stem cells (MSCs).

The benefit of using these particular MSCs is that they can be acquired from a Master Cell Bank of iPSCs derived from a single healthy blood donor – limiting donor- and expansion-dependent variability as well as contamination from non-target cells.

A number of stem cells/MSCs have demonstrated anti-inflammatory and immunomodulatory properties. However, the fibrosis associated with chronic organ injury can often act as a barrier to the therapeutic/anti-remodelling efficacy of MSCs, impacting on their ability to survive, home to the site of injury and integrate with resident cells post-administration.

The iPSC-derived MSCs appear to have similar effects to fetal fibroblasts, which can facilitate wound healing in the absence of fibrosis.

Combined with their demonstrated anti-inflammatory effects, they were also able to normalise airway hyperresponsiveness that results from ongoing airway inflammation and airway remodeling/ fibrosis.

The study found even more benefit when stem cells were administered intranasally versus intravenously. What does this finding tell you?

It tells us that the direct administration of these cells into the targeted/injured organ has improved efficacy over their systemic administration. Having said that, after systemic delivery of MSCs, these cells initially become entrapped within the lungs – which is advantageous for using them as treatments for respiratory disorders.

You’ve got a special interest in airway/lung fibrosis. What are the opportunities with stem cells on this particular component of lung disease?

There are no effective cures for airway/lung fibrosis. With respect to asthma, current therapies including corticosteroids and eta-agonists are directed at symptomatic management rather than disease regression. Some people with asthma are also resistant to corticosteroid therapy.

Hence, these iPSC-derived MSCs offer the unique opportunity to reverse several features of airway remodelling/fibrosis and related airway hyperresponsiveness.

 From bench to bedside – what are the next steps in application of your findings?

We are currently comparing and combining these iPSC-derived MSCs with a clinically-used corticosteroid to determine how effective these stem cells are compared to current standard of care and whether they may augment the actions of corticosteroids.

Understanding their mode of action and determining optimal ways in which we can deliver these stem cells to the human lung will be the next steps.