Use of Intrathecal Administration MSCs for Asthma

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), airway obstruction, and remodeling. Allergic asthma is characterized by T helper 2 (Th2) inflammation, which usually responds well to inhaled corticosteroids. 

In some cases, patients develop severe asthma refractory to high-dose inhaled corticosteroids which shows a need for better and alternative treatment methods. 

The use of mesenchymal stem cells (MSCs) is one of the treatment methods that has been evaluated for multiple immune-related conditions. 

MSCs act as immune modulators and affect various immune cells by inhibiting the proliferation of CD4+ and CD8+ T cells, modulating the plasticity of the role of T cells, including regulatory T cells (Tregs). They also play an important role in regulating macrophage activation. Macrophages are the most common type of immune cells in the airway. 

Recently, a group of researchers evaluated the effects of MSC administration in a mice model of asthma. Their results were published in the journal Scientific Reports. 

Local Regulation of Lung Macrophages 

For the study, the team administered human umbilical cord MSCs intrathecally. After administration of the ucMSCs, the researchers observed a decreased AHR and airway inflammation observed in the asthma model. 

Immune cell infiltration in the bronchi and the blood vessels were reduced in the histological analysis of the group that received the ucMSCs. They also observed that the number of eosinophils in the lungs was significantly decreased. 

The study successfully showed that intrathecal MSC administration modulated lung macrophages and ameliorated airway inflammation and airway hyperresponsiveness. The researchers observed a reduction in the number of dendritic cells and macrophages, suppression of inflammation, and amelioration of airway remodeling. 

Intravenous administration of MSC is the other more commonly used and studied route of administration. This route shows a systemic effect, targeting circulating monocytes, while the intrathecal administration showed to exert its effects through regulatory effects more locally on lung macrophages. Both could be used to exert a greater benefit both increasing the regulation of the immune response locally and systemically. Further studies are needed to evaluate the effect in humans of intrathecal administration of ucMSCs. 

Source:

Mo, Y., Kang, H., Bang, JY. et al. Intratracheal administration of mesenchymal stem cells modulates lung macrophage polarization and exerts anti-asthmatic effects. Sci Rep 12, 11728 (2022). https://doi.org/10.1038/s41598-022-14846-y 

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