One of the ongoing themes in stem cell research is the discovery that numerous tissues thought to be static or poor at regeneration are in fact generating new cells, and can in fact naturally regenerate under some circumstances. If the rudiments of these regenerative mechanisms exist, then why not build therapies based on reliably activating and steering them? Or so the thinking goes. At the present time work hasn't progressed much past discovery and experimentation, even for nerve tissues where the crucial discoveries that neurogenesis occurs in adults were solidified and accepted fifteen years ago. Most of the progress in the broader field of regenerative medicine to date has been a case of improving on regenerative mechanisms that have long been well recognized and are consistently at work in ordinary adults. That will change soon enough, however, as improved technologies and capabilities in working with cells are leading to rapid progress in all areas of cell research. The equipment and knowledge present in the labs of today is far advanced over that of even a decade ago, and the pace is picking up.
Here is a great example of the sort of discoveries taking place in recent years regarding the regenerative capabilities of tissues that normally recover from damage only poorly. In this case the focus is on the lung. Like much of this work, it seems very promising - that there are mechanisms that could with just comparatively simple manipulations greatly enhance the normal state of tissue regeneration. "Comparatively simple" is usually still a major research project in any form of cell biology, unfortunately, but this and similar results in other tissues show the path ahead. Regenerative medicine will undergo a great deal of improvement in near future:
The idea that the lung can regenerate has been slow to take hold in the biomedical research community, in part because of the steady decline that is seen in patients with severe lung diseases like chronic obstructive pulmonary disease (known as COPD) and pulmonary fibrosis. Nevertheless, there are examples in humans that point to the existence of a robust system for lung regeneration. Some survivors of acute respiratory distress syndrome, or ARDS, for example, are able to recover near-normal lung function following significant destruction of lung tissue.
Mice appear to share this capacity. Mice infected with the H1N1 influenza virus show progressive inflammation in the lung followed by outright loss of important lung cell types. Yet over several weeks, the lungs recover, revealing no signs of the previous lung injury. Using this mouse model system, [researchers] previously identified a type of adult lung stem cell known as p63+/Krt5+ in the alveoli found within the lung.
The research team reports that the p63+/Krt5+ lung stem cells proliferate upon damage to the lung caused by H1N1 infection. Following such damage, the cells go on to contribute to developing alveoli near sites of lung inflammation. To test whether these cells are required for lung regeneration, the researchers developed a novel system that leverages genetic tools to selectively remove these cells from the mouse lung. Mice lacking the p63+/Krt5+ lung stem cells cannot recover normally from H1N1 infection, and exhibit scarring of the lung and impaired oxygen exchange - demonstrating their key role in regenerating lung tissue. The research team also showed that when individual lung stem cells are isolated and subsequently transplanted into a damaged lung, they readily contribute to the formation of new alveoli, underscoring their capacity for regeneration.
Lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and the possibility of regenerative medicine has lacked empirical support. However, it is clinically known that patients who survive sudden, massive loss of lung tissue from necrotizing pneumonia or acute respiratory distress syndrome often recover full pulmonary function within six months.
Correspondingly, we recently demonstrated lung regeneration in mice following H1N1 influenza virus infection, and linked distal airway stem cells expressing Trp63 (p63) and keratin 5 (Krt5) to this process. Here we show that [these cells] undergo a proliferative expansion in response to influenza-induced lung damage, and assemble into nascent alveoli at sites of interstitial lung inflammation.