Scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA coated tiny gel beads with stem cells from lungs, allowing them to gradually grow into air sacs similar to those found in human lungs.

These 3D lung organoids have enabled the advancement of medical science, and one such aspect is the study of the pathology of idiopathic pulmonary fibrosis (IPF), which before the development of this technique, has long eluded researchers.

Breakthrough in research

Lead author and associate professor Brigitte Gomperts at UCLA paediatric haematology and oncology department played down their findings, saying that “While we haven’t built a fully functional lung, we’ve been able to take lung cells and place them in the correct geometrical spacing and pattern to mimic a human lung.”

IPF is a chronic lung disease where scarring would occur in the lungs. This scarring renders the lungs thick and stiff, and over time results in the progressive deterioration of shortness of breath, and a lack of oxygen to the brain and vital organs.

The prognosis is poor and most individuals would expect to experience three to five years of life expectancy. The exact pathology is yet unknown; family history, cigarette smoking, and exposure to certain types of dust are all known risk factors.

Before the development of the 3D model, the analysis of the genetic mutations or drugs on lung cells are based on 2D cultures. However, scientists have been unable to model the pathology of IPF in the lab, as the cell cultures derived from IPF patients all are tested to be healthy. This inability to model IPF poses unique challenges in understanding and treating this disease.

Growing lungs in a petri dish

Gomperts and her team used cells from adult lungs and created stem cells. The stem cells were then coated onto sticky hydrogel beads, and thereafter partitioned into small wells measuring 7mm across. In each well, the lung cells grew around the beads, and gradually linked and formed an evenly distributed 3D pattern. The results are then compared with real sections of human lung.

First author Dan Wilkinson, graduate student in the Department of Materials Science and Engineering, explained that “The technique is very simple. We can make thousands of reproducible pieces of tissue that resemble lung and contain patient-specific cells.”

The breakthrough was when Wilkinson and Gomperts modified these cells at the molecular levels, the lungs developed scars similar to those seen in the lungs of people who have IPF, something that cannot be done using the existing 2D cultures.

Hope for IPF patients

Currently IPF sufferers only hope is in lung transplantation. In Singapore, the procedures for lung transplantation is rare; even with the Human Organ Transplantation Act, only about ten such procedures have been carried out. Part of the challenge lies in sourcing for suitable donors, which can only be from recently deceased individuals with healthy lungs.

This breakthrough in lung modelling has enabled the researchers to study how IPF and other lung diseases work biologically, and opens up many opportunities for the testing of possible cures for these debilitating lung diseases.

A personalised treatment regime can be designed with the patient’s own cells using this technique. Due to its relative ease of creating many tiny organoids at once, this enables doctors to analyse the effect of many drugs simultaneously. “This is the basis for precision medicine and personalised treatments,” Gomperts added. MIMS

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