Scientists create lung cells in a few days, not weeks

Japanese researchers have developed a method that can produce lung cells from ordinary mouse fibroblasts in just 7 to 10 days, thus eliminating more than half of the time required for this transformation.

This technology completely bypasses stem cell technology and can accelerate the treatment of severe respiratory diseases such as interstitial pneumonia and chronic obstructive pulmonary diseases.

Breakthrough centers on direct reprogramming, where scientists use specific genes to directly convert one cell type into another without the need for complex intermediate steps. This approach has significant advantages over current methods that rely on inducing pluripotent stem cells.

Four gene formulas

The Nagoya University team identified the precise combination of four genes NKX2-1, FOXA1, FOXA2 and GATA6 that can reprogram fibroblasts into alveolar epithelial type 2 (AT2) cells. These specialized lung cells produce surfactants and serve as maintenance personnel for damaged lung tissue.

“In 2006, induced pluripotent stem cell (IPSC) technology produced AT2 cells in about a month, but this approach is expensive and has the risk of tumor formation and immunosuppression.”

New approaches can address these limitations head-on. If the traditional IPSC method takes about 30 days and assumes tumor risk, direct reprogramming will produce functional lung cells within a time of low cancer potential.

Excellent efficiency

The researchers achieved impressive results using a three-dimensional culture system:

• About 4% of treated cells become lung-like within 10 days
• The cells produced show characteristic lung cell structures, including lamellar bodies
• Cells maintain their performance through multiple growth cycles
• Transplanted cells successfully integrate into damaged mouse lungs

Real-world test

The team tested lab-grown cells in lung-injured mice similar to human lung fibrosis. 42 days after transplantation, the reprogrammed cells were successfully implanted into the lung tissue and began to distinguish the cell types required for tissue repair.

It is worth noting that some transplanted cells develop into alveolar epithelial type 1 cells, which is essential for gas exchange, which is the basic process that makes us breathe. This suggests that reprogrammed cells retain the flexibility required for integrated lung repair.

The study revealed important technical details not highlighted in the initial report: the researchers used a complex three-dimensional culture system and combined with fluorescently activated cell classification to achieve its high success rate. This approach to methodology proves crucial to isolating the desired cell type from the mixed population.

Clinical Commitment

What makes this study particularly exciting is its potential for personalized medicine. Since the technology starts with the patient’s own fibroblasts, it theoretically avoids the immune rejection problems that plague many transplant therapies.

“To overcome these shortcomings, we focus on direct reprogramming,” Ishii notes. “The direct reprogramming method produces AT2-like cells in just 7 to 10 days, with a low tumor risk and autologous use potential.”

Currently, treatment for diseases such as idiopathic pulmonary fibrosis is still limited, and lung transplantation is usually the only option for end-stage diseases. However, a shortage of donor organs means that about 20% of patients die while waiting for transplants.

Next step

The research team acknowledged that there were still significant obstacles before clinical application. Most importantly, the technique is demonstrated only in mouse cells – human cells may require different genetic combinations or culture conditions.

ISHII concluded: “In this study, we successfully reprogrammed fibroblasts directly into mouse AT2-like cells. We now aim to explore the application of this technology in human cells, with the ultimate goal of developing safe regeneration therapies using the patient’s own fibroblasts.”

This work represents a meaningful step towards regenerative lung medicine, which could bring hope to millions of respiratory diseases that are currently incurable.

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