Advances in stem cell research offer unprecedented opportunities to develop new treatments, disease models, and drug screens for previously untreatable conditions. These discoveries have captivated the imagination of the lay press and have inspired hope in patients, clinicians, and scientists. Inevitably, in an emerging new field, there are false starts that accompany promising discoveries. If rigorous researchers in the field have difficulty discerning hype from hope, what is a busy clinician to do when confronted with basic questions, such as: “Is stem cell therapy available for my lung disease?” or “Shall I bank my baby's cord blood in case he/she develops cystic fibrosis or emphysema?”. This chapter is designed to describe the quickening pace of stem cell and regenerative medicine research related to lung disease and to place the latest discoveries in a historical context, before discussing future prospects.
Stem cells have been found in an increasing number of tissues whose biology is characterized by rapid turnover of differentiated cells. In these tissues, for example, blood, skin, and intestine, a stem cell hierarchy has been described where rare stem cells proliferate occasionally, giving rise to stem cell daughters or to progenitors that can proliferate rapidly, and differentiate into mature cells required for the function of that tissue. These properties of self-renewal and differentiation are the classic hallmarks of stem cells, and their importance in homeostatic maintenance of the blood, skin, and intestine, are well accepted.1–3 These features also make stem cells attractive vehicles for clinical applications such as the reconstitution of injured or diseased tissues. Several decades of research focused on animals and humans, including the seminal bone marrow transplantation work of Till and McCullough4 has rigorously proven, for example, that the hematopoietic stem cell, a cell that comprises 1 in 10,000 bone marrow cells, can be delivered to a recipient by simple intravenous infusion, reconstituting all cells of the bone marrow and circulating blood for the life-time of the recipient.1
Given the virtually unlimited self-renewing capacity and blood differentiation repertoire of hematopoietic stem cells, most pulmonologists are surprised to learn that cells of similar capacity have not been reproducibly proven to exist in the lung and may not be necessary for the homeostasis of an organ with a quiescent epithelium that contrasts with the rapidly self-renewing epithelia of intestine and skin.
Lung Epithelial Responses to Injury
Because the unperturbed adult lung epithelium displays remarkably slow cell turnover, the post-injury or disease responses of human or animal lung have been studied to elucidate both the proliferation potential and differentiation repertoire of various lung cell types. These injury models have been used to search for potential specialized lung cells that might exhibit stem cell properties, such as self-renewal and multipotent differentiation (reviewed by Rawlins and Hogan).5 Beginning ...