Reconstructing the lung stem cell niche in vitro

Lungs are constantly exposed to a variety of environmental hazards and undergo injury. In response to injury, a reservoir of lung stem cells undergoes rapid self-renewal, proliferation, and subsequent differentiation in order to repair, regenerate, and preserve tissue homeostasis. Though significant advances have been made in the field of lung stem cells, stem cell engineering, and lung disease molecular pathogenesis, still lung diseases are the leading cause of death globally. Lung transplantation though promising but unavailability of donor lungs is a major issue; hence, regenerative medicine can bring promising solutions for lung diseases. Stem cells can help repair and regenerate lungs after injury but can maintain, self-renew and differentiate only in the presence of a specialized microenvironment called the “stem cell niche.” The niche offers biochemical, biophysical, and physiological cues that interact with stem cell's intrinsic genetic and epigenetic signaling and regulate stem cell physiology. Hence, recapitulating the lung stem cell niche is critical for recreating and comprehending stem cell and regenerative biology. The niche function can be played by multiple cell types, including epithelial, mesenchymal, endothelium, and immune cells. A niche can be created in vitro by using appropriate extracellular matrix material, neighboring cells, supplemented with niche-associated factors, and grown in a three-dimensional geometry that offers molecular and structural stability to the stem cells. Recent data suggest that a diseased niche or altered niche can play a role in the pathogenesis of several lung diseases. Artificial niche creation is crucial for understanding niche-stem/progenitor cell interaction, stem cell regulatory mechanisms, niche modulating small molecule screening, niche-bioengineering, the discovery of novel therapeutic interventions, and regeneration of replacement tissues. Considering the progress made in the field of stem cell biology, nanotechnology, and material chemistry may help recapitulate the lung stem cell niche and help translate into effective therapies in the near future.