Transplanting transgenic macrophages expressing human antiprotease alpha-1 antitrypsin (AAT) into the lungs of mice can be a source of functional AAT protein, researchers in Germany demonstrated. They made the macrophages from mice transgenic for AAT, ie, expressing human AAT, using a lentiviral vector. 

The researchers also demonstrated that macrophages derived from human cord blood cells and differentiated in vitro could express and secrete AAT when transduced with their lentiviral vector carrying the gene encoding for AAT. This finding, they said, demonstrates the applicability of their lentiviral vector in human cells.

Their aim was to investigate whether transplanting macrophages transgenic for AAT into the lungs could be a therapeutic approach for emphysema that occurs in AAT deficiency (AATD).

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In the past, researchers have shown that directly transducing the alveolar macrophages of mice with a lentivirus carrying the gene encoding for AAT led to protective AAT levels in the lungs of the animals and delayed the development of emphysema.

Here, the team led by Thomas Moritz wanted to investigate whether transplanting macrophages transgenic for AAT into the lungs could yield enough AAT production.

First, they developed a mouse alveolar macrophage cell line that is able to secrete high levels of AAT. They also differentiated cells obtained from the bone marrow of the animals and from human cord blood cells into macrophages and modified them to produce AAT. 

The AAT protein secreted from these cell lines had the right glycosylation pattern. They also had elastase-inhibitory and anti-apoptotic properties. (Elastase is a protease that can digest connective tissue elements and too much of it can be associated with emphysema. where the inner walls of the alveoli in the lungs weaken and break.)

Macrophages differentiated from the bone marrow had normal morphology, surface phenotype, and function. The researchers were able to successfully engraft these cells into alveolar macrophage-deficient mice and they were able to detect human AAT in the fluid lining the lung epithelium of the transplanted animals.

The study appeared in Gene Therapy on July 19, 2021.

AATD is an autosomal codominant genetic disease associated with early-onset emphysema as well as hepatic failure. There is currently no cure for it.


Janosz E, Hetzel M, Spielmann H, et al. Pulmonary transplantation of alpha-1 antitrypsin (AAT)-transgenic macrophages provides a source of functional human AAT in vivo. Gene Ther. Published online July 19, 2021. doi:10.1038/s41434-021-00269-3