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Profile: Durable Alveolar Engraftment of PSC-Derived Lung Epithelial Cells into Immunocompetent Mice

By September 20, 2023No Comments

Photo courtesy of the Kotton Lab. Image includes senior author Dr. Darrell Kotton (front, right), and interviewees Dr. Michael Herriges (middle, fourth from right) and Martin Ma (back, fourth from left). 

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This week we profile a recent publication in Cell Stem Cell from the lab of Dr. Darrell Kotton at Boston University. We interviewed Dr. Michael Herriges, primary author and a postdoc in the Kotton Lab, and Martin (Liang) Ma, an author and MD/PhD student in the Kotton Lab. 

Can you provide a brief overview of your lab’s current research focus?

Herriges: The Kotton Lab is currently interested in advancing our understanding of lung disease and developmental biology with a focus on stem cell biology and the development of treatments such as cell engraftment and gene therapy.

What is the significance of the findings in this publication?

Ma: These studies demonstrate the feasibility of engrafting functional engineered stem cells into syngeneic recipient lungs without the need of immunosuppression and could serve as a steppingstone for follow-up work with the ultimate goal of developing an autologous cell-based therapy for respiratory diseases. We hope one day we will not only have an approach to reconstitute healthy tissue in common respiratory diseases characterized irreversible tissue damage such as COPD and pulmonary fibrosis, but also put options on the table for patients who suffer from orphan diseases caused by rare mutations in the lung.

What are the next steps for this research?

Herriges: Moving forward, we would like to transplant these cells into mouse models of genetic pulmonary diseases in order to test whether they can prevent or reverse the progression of these diseases.

Was there anything particularly challenging that stood out to you or that you had to troubleshoot?

Herriges: The most challenging parts of this work revolved around optimizing the protocols to generate the right donor cells. It took a lot of time to find the right cell type and then optimize a new protocol to efficiently generate that cell through directed differentiation of PSCs.

What kind of impact do you hope your research will have?

Ma: We hope that the ability to repair or regenerate alveoli with cells engineered from stem cells will open up new approaches for repairing lungs damaged by a variety of injuries or genetic mutations in the future. While treatment of lung diseases, such as emphysema, pulmonary fibrosis, and COVID-19 with our approach will take a lot more research, we are hopeful that those with gene mutations that cause damage to lung alveoli, such as children or adults with inherited or familial forms of interstitial lung disease might be treatable in the future with this type of approach.

Where do you see this research going in the next five/ten years?

Herriges: In the next five/ten years this research will hopefully progress towards modelling cell therapy for genetic diseases. It is also our hope that we can adapt some of these techniques towards developing cell engraftment in larger species as a steppingstone towards the ultimate goal of cell-based therapy for humans.

This research is funded by: the NHLBI, Boston University Kilachand Multicellular Design Program Accelerator Grants, and an Allen Distinguished Investigator grant from the Paul G. Allen Family Foundation.

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