Lung Stem Cells
LAY REVIEW

Introduction

Stem cell research is an up and coming scientific field that is constantly redefining the most primitive origins of life. Stem cells researchers believe that stem cells are the common precursors of all cells throughout the human body – the immune cells, blood cells, neurons, and all of the cells that make up solid organs. Stem cells, in essence, are the hierarchical parent cell. In order for stem cells to produce specific types of cells, they undergo a process known as differentiation, in which the parent stem cell divides into one daughter cell and one replica of the original stem cell. This process, by which two non-identical daughter cells are derived is known as asymmetrical division and displays one of the classical hallmark identifiers of stem cells, self-renewal. Self-renewing ability is vitally important as stem cells are quantitatively conserved in the body and must therefore be capable of replicating limitlessly in order to maintain a large stem cell population.

The limitless potential of stem cells to derive all the components that make up the human body and their ability to self-renew have placed stem cells in the spotlight in regenerative tissue therapy (Kotton, 2004). In fact, many researchers believe that harnessing the power of stem cells will allow doctors the ability to re-grow missing limbs, replenish poor immune systems and replace failing organs. Like other stem cells, lung stem cells most likely know how to differentiate in specific cell subtypes through cues received from the environment around them. These cues may come from a wide range of signaling molecules such as growth factors, cytokines and chemokines (chemical signaling mechanisms). Stem cells rely heavily on their environmental niche for proper execution of the differentiation process. The cues that lung tissue renewal relies on are not currently defined (Neuringer, 2006).

There are few medical fields were the power of stem cell research would aid doctors as much as in pulmonary therapeutics. The lung begins as a group of sacs of germ cells early in development, in a formation known as a blood island. These sacs of cells soon begin to branch out vascular structures and form the highly complex lung which continues to develop in the fetus. The lung is a highly complex organ that is thought to be comprised of over 40 different types of cells and researchers believe that these cells are derived from common precursor cells, capable of differentiating into all that cells that compose the lung.  In theory, by harnessing the power of the pluripotent –able to differentiate into a range of cell types - lung stem cell progenitor, researchers may be able to learn more about lung formation and how to use this knowledge in therapeutic approaches for lung injury.

The Lung Stem Cell and Therapeutics

There are many lung-associated diseases that could be alleviated by discoveries in lung stem cell research. Many cancer therapies rely on the ablation, or total wipe-out, of pre-cancerous tissue. Following harsh chemotherapeutics or radiating therapeutics with the replenishment of patient-identical immune cells and lung tissue would be ideal methods for helping the patient recover quickly and safely. By using the patient’s own stem cells, one avoids serious complications such as donor rejection caused by Graft Versus Host Disease. Cancerous lung tumors, such as adenocarcinoma, affect 35% of all cancer patients each year (Majka 2005).

Other pulmonary diseases that may see benefit from stem cell research include emphysema, a disorder affecting the alveoli (tiny air sacs) of the lungs. The transfer of oxygen and carbon dioxide in the lungs takes place in the walls of the alveoli. In emphysema, the alveoli become abnormally inflated, damaging their walls and making it harder to breathe. Pulmonary hypertension and fibrosis - chronic inflammation of the lung tissue - are other medical pathologies that could see direct benefit from lung stem cell research.  Additionally, scientists have very recently uncovered information that Severe Acute Respiratory Syndrome, or SARS, is caused by a virus which targets specific sets of stem cells in the lung. By targeting these cells for medicinal therapies, it may be possible to lessen the lethality of SARS (Ling 2006).

Current Issues in Lung Stem Cell Research

There is, however, a long journey ahead of stem cell researchers before any of the current information can be safely put to therapeutic use. Lung stem cell research, and stem cell research as a whole, is in its infancy.  Stem cell science is very difficult because the cells scientists must work with are very premature and are not as easily classified as fully mature cells (Kotton 2005). While scientists work to discover cell progenitors and precursors, methods that identify specific types of stem cells have been shown to be not entirely error-proof. It is for this reason that great precaution must be taken to use rigorously tested and standardized experimental methods to avoid contradictory results and prematurely published results. Unfortunately many lung stem cell researchers have already experienced the problems of the field first hand, releasing publications that were later refuted by newer evidence.

In addition to these problems, the lung itself is a highly complex organ. The lung develops from cells derived from all the various germ layers of the body – the endoderm, mesoderm and ectoderm. While subsets of cells have been identified that may act as lung progenitors for particular subsets, such as Clara Cells which comprise parts of the lung airway passages, the overall picture has not been solved (Neuringer, 2006). It appears that a highly orchestrated dance takes place in which cells from all three germ layers perform a highly conserved choreography that aids in the embryonic development of the lung. Other debates revolve around the actual origin of tissue specific stem cells. The traditional view of stem cell renewal is that, during development, self-renewing tissues possesses self-renewing tissue specific stem cells - adult somatic stem cells (Neuringer, 2006). Recent data suggests that this may not be the case and that stem cells may receive cues in the bone marrow and upon circulation, home to specific targets to aid in tissue renewal. These puzzles continue to elude researchers as this piece is written.

Promising Data

While these setbacks may seem daunting, much has been accomplished in the lung stem cell field. Within the lung, cells have been identified that are capable of restocking the immune cells that comprise our bodies’ infectious defense system. These cells may be very important in comprising our defense system against airborne pathogens. Additionally, these cells have been found capable of reconstituting the bone marrow of deficient mice (Summer, 2005). The bone marrow is the niche in which many types of immune cells and stem cells reside. Cells in the lung have also been found that are capable of forming vascular structures upon laboratory culture dishes. These cells may be very important in the formation of endothelial aspects of the lung – the lung provides vascular structure for the gas exchanging system necessary to oxygenate our body’s blood supply. In fact, these cells were able to form functional bronchial epithelium which shows just how powerful and capable lung stem cells actually are, even ex-vivo, or out of the human body (Coraux, 2005).

In addition to these advances scientists believe they may have found possible sources of lung stem cells, or lung cell progenitors. Using advanced scientific techniques such as immunochemistry, scientists are able to identify specific subsets of cells. Immunochemistry, in essence, allows scientists to probe for the expression of specific proteins or other markers. If a cell types expresses a desired protein, for example, the cell could further be analyzed by culturing it on specific media for the cell type, growing it to a large quantity and then examining the cell’s activity. In lung stem cell research, a specific marker, such as Oct-4, is highly important for stem cell renewal. By probing for Oct-4 expression, scientists have uncovered cells residing in the lung that may actually be a source of lung stem cell (Ling, 2006)

Conclusion

There are many ways which stem cells will begin to affect modern day therapy. Stem cells, barring legality issues, will become a focal point of curative medicine in almost every field, from neuroscience to dermatology. This is due to their multi-potent capability for regeneration of injured or deficient tissue. The beauty of stem-cell based medicine lies in the fact that doctors can safely avoid modern transplantation barriers, such as host-donor matching while providing an even more powerful source of healing to the patient. Researchers have already uncovered enormous amounts of information about the origins of many of the fully formed cell-types in our body and are making great advances in lung stem cell research as well. The future of lung stem cell research is both exciting and promising, with only the human mind as the barrier to a plethora of possibilities.

References

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Acknowledgements

This review was prepared by the following graduate students in the Stem Cell Biology Class, Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey:

Tara Gooen, Joel Schneider, and James Sturzione (in alphabetical order)

Teaching Assistant: Kathy Trzaska