GDF11 secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis

Nagy, A.; Guo, L.; Duchesneau, P.; Sawula, E.; Jong, E. D.; Li, C.; Waddell, T.

doi:10.1101/2024.09.06.611670

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bioRxiv · 10.1101/2024.09.06.611670

GDF11 secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis

Nagy, A.·Guo, L.·Duchesneau, P.·Sawula, E.·Jong, E. D.·Li, C.·Waddell, T.

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Abstract

Here, we present a combination of cell and gene therapy that harnesses the regenerative properties of GDF11 in age-related pulmonary fibrosis. Our genome-edited FailSafeTM-GDF11 mouse ESC line provides controlled proliferation and efficient derivation to lung progenitors while inducibly expressing GDF11. When these cells were transplanted into bleomycin-injured aged mice, they acted as a source of reparative cells, restoring the damaged alveolar epithelium. Furthermore, the transplanted cells acted as an "in situ factory", enabling the production of GDF11 in response to the inducer drug. This approach attenuated age-associated senescence and led to the successful resolution of fibrosis. Our study presents a promising method for treating pulmonary fibrosis. Additionally, this approach offers a versatile tool that can be expanded to incorporate other regenerative and anti-aging factors. This helps overcome limitations such as high production costs and a short half-life of therapeutic factors. One of the strengths of our system is its ability to allow precise regulation of factor-expression when needed to address specific aging phenotypes.

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Nagy, A., Guo, L., Duchesneau, P., Sawula, E., Jong, E. D., Li, C., Waddell, T.. 2024-09-07. GDF11 secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis. https://doi.org/10.1101/2024.09.06.611670

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