Alpha-1-Antitrypsin expressing Mesenchymal Stem Cells (MSC-AAT) for the treatment of severe cases of COVID-19 infection

Abstract

With the outbreak of the COVID-19 pandemic, the search for specific forms of therapy began. Especially severe courses with multiorgan failure and the resulting long-term damage pose a particular challenge. The better understanding of immunological correlations in the context of the infection allowed the identification of specific infection pathways of the virus into the body cells as well as mechanisms in the development of a fatal cytokine release syndrome (CRS). Early clinical studies with mesenchymal stem cells could show a side-effect free modulating effect on this excessive immune reaction. In the severely affected regions of Northern Italy, coincidence with a latent congenital alpha-1 antitrypsin deficiency was observed. In vitro experiments demonstrated an anti-infective and immunoregulatory effect of alpha-1-antitrypsin. Low plasma levels of this acute phase protein appear to play a central role in the development of severe and fatal disease. The combination of both principles in a genetically engineered stem cell with the ability to express alpha-1-antitrypsin seems logical. This cell therapy with its specific effect could be used especially in patients with a severe course of disease and a cytokine release syndrome.

Mesenchymal Stem Cells as a Gene Delivery Tool: Promise, Problems, and Prospects

“…The alpha-1 antitrypsin (AAT) protein is acknowledged for being one of the key players in the acute phase anti-inflammatory response [108]. Therefore, MSCs engineering appears to be a promising strategy to overexpress the AAT protein, not only to treat AAT deficiency, but also to augment AAT in patients with normal plasma levels of AAT [109]. This approach is quite flexible as patients would benefit from the versatile secretome of MSCs in addition to the expression of AAT protein [110].…”

Insights into the potential role of alpha1‐antitrypsin in COVID‐19 patients: Mechanisms, current update, and future perspectives

“…Moreover, MSC engineering appears to be a promising strategy to overexpress AAT that could be used to treat AATD, or to augment AAT in patients with normal AAT plasma levels 18 . This approach is quite flexible as patients might benefit from the versatile secretome of MSCs, in addition to the AAT expression 19 …”