Lab-grown lungs successfully transplanted into mice

Transplanted HLO-scaffold constructs engrafted, grew and possessed airway-like structures.

Keyword: HLOs-Human Lung Organoids, PLG- poly(lactide-co-glycolide)  

Fig: (A) PLG scaffold are 5 mm in diameter with honeycomb-patterned architecture. (B) The majority of Di-O labeled 1d HLOs (green) remained at the surface of the scaffold with a few organoids descending toward the middle of the scaffold. Inset shows aerial view of the scaffold with 1d HLOs (green) scattered throughout. (C) 1d HLOs settled within the pores of the scaffold. Scale bar represents 100 µm. (D) PLG scaffolds were seeded with 1d HLOs and cultured for 5 to 7 days in vitro in media supplemented with FGF10. The HLO-laden scaffolds were then transplanted into the mouse epididymal fat pad and harvested at 8 weeks. (E) HLO-scaffold (dotted line) was placed in mouse epididymal fat pad. (F) Transplanted HLOs (tHLOs) ranged from 0.5 cm to 1.5 cm in length. (G) The average number airway-like structures that were NKX2.1+ ECAD+ out of all ECAD+ structures was 86.19% +/- 4.14% (N = 10, error bars represent SEM). (H) H&E of tHLOs showed airway-like structures (right two panels, low and high mag) and pockets of cartilage (left panel). Scale bar at low mag represents 200 µm and high mag 100 µm. (I) Airway-like structures outlined by ECAD (white) expressed the lung marker NKX2.1 (green). Scale bar represents 50 µm. (J–K) Both the epithelium (β-CAT, red) and mesenchyme expressed the human nuclear marker, HUNU (J, green) and the human mitochondrial marker huMITO (K, green). Scale bars represent 50 µm in J–K and 10 µm in high mag image in K.

DOI: http://dx.doi.org/10.7554/eLife.19732.003

Researchers at the University of Michigan have transplanted lab-grown mini lungs into immunosuppressed mice where the structures were able to survive, grow and mature. Respiratory diseases account for nearly 1 in 5 deaths worldwide, and lung cancer survival rates remain poor despite numerous therapeutic advances during the past 30 years. Now, the researchers attempted to transplant the miniature lungs into mice, an approach that has been widely adopted in the stem cell field. 

Researchers characterized the transplanted mini lungs as well-developed tissue that possessed a highly organized epithelial layer lining the lungs.

One drawback was that the alveolar cell types did not grow in the transplants. Still, several specialized lung cell types were present, including mucus-producing cells, multiciliated cells and stem cells found in the adult lung.

Ref:: Briana R Dye et al., (2016) A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids, eLIFE.

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DOI: 10.7554/eLife.19732