Stem cells and cell therapies for cystic fibrosis and other lung diseases

Abstract

This review will critically evaluate recent findings suggesting that embryonic stem cells and stem cells derived from adult tissues, including bone marrow and umbilical cord blood, may be utilized in repair and regeneration of injured or diseased lungs. This is an exciting and rapidly moving field that holds promise as a novel therapeutic approach for cystic fibrosis and other lung diseases. However, while early studies suggested substantial lung remodeling, particularly with bone marrow-derived cells, more recent findings suggest that engraftment of adult marrow-derived cells in lung is a rare event of uncertain significance. Most recently, it has been suggested that a more relevant role of adult marrow-derived stem cells in lung is modulation of local inflammatory and immune responses. This review will also describe recent advances in understanding of local stem and progenitor cells in lung and their roles in lung development and repair.

Figure 1

Schematic of endogenous, embryonic, and adult stem cells that potentially participate in lung development, injury, repair, and regeneration.

Figure 2

Detection of Cftr expression in female Cftr KO mouse lungs following transplantation with male GFP stromal marrow cells. C,F) Donor derived (Y chromosome, red), Cftr positive (green), and cytokeratin positive (blue) cells, are indicated by light blue arrows in airway walls of lungs assessed 1 week after transplantation. Images from two separate recipient mouse lungs are depicted. A,D) and B,E): The same photomicrographs are shown after removal of the blue and the green channel respectively, to show co-expression of Cftr and cytokeratin by the donor-derived cells. Original magnification 1000X. Figure reprinted with permission from Loi et al Am J Resp Crit Care Med 2006; 173:171 [21].

Figure 3

Endogenous regenerative microenvironments in the bronchiolar epithelium of the mouse. In situ hybridization for CCSP mRNA (white autoradiographic grains) was used to identify regions of regenerating epithelium following naphthalene-mediated progenitor cell depletion. Regenerative zones of neuroepithelial bodies were identified located at branch points in the airways (red ovals) and at the bronchoalveolar duct junction (green ovals). Figure courtesy of Susan Reynolds and Barry Stripp, University of Pittsburgh and reprinted with permission from Weiss et al Proc Am Thoracic Soc 2006;3:193 [7].