Left ventricular assist, portable dialysis devices, and extracorporeal membrane oxygenation (ECMO) devices are good examples of advanced biomedical engineering approaches that can augment defective organ functions for both short and sometimes more prolonged time periods ( 12). A third broad area of regenerative medicine is the development of adjunct devices to replace or augment defective tissue or organ function. Several developing strategies such as “organ on a chip,” organoid culturing, three-dimensional (3D) bioprinting, and de- and recellularization have provided novel approaches, particularly with respect to lung ( 7– 11). Although there has been success with tissues such as skin, muscle, and bone, this has been a challenge for lung ( 5). A second broad regenerative medicine approach is that of growing tissues and organs in the laboratory for implantation when the body cannot heal itself. A broader field of antiinflammatory actions of MSCs, and a primary focus of this review, has also been explored with the primary goal of decreasing inflammation and injury without necessarily promoting structural repair in both preclinical lung disease models and in clinical trials in lung diseases ( 5, 6). More recently, and as further discussed below, cell-based therapies, utilizing systemic or intratracheal administration of a variety of cell types including endogenous lung progenitor cells, induced pluripotent cell–derived lung epithelial cells, endothelial progenitor cells, and allogeneic mesenchymal stromal cells (MSCs), have been postulated to promote structural and functional regeneration of gas exchange ( 3, 4). Use of pharmacologic means to stimulate reparative postnatal lung growth, for example, administration of retinoic acid, although promising in mice, did not have beneficial effects in clinical trials ( 2). Arguably, a means to stimulate controlled alveolar and airway regeneration in situ in patients with chronic obstructive pulmonary disease (COPD) and other destructive lung diseases such as idiopathic pulmonary fibrosis would be a significant advance. This is particularly applicable to complex tissues such as lung, in which limited endogenous reparative mechanisms can be overcome by either the severity of illness or the chronicity of the insult that is, cigarette smoking. One of these is stimulating the body’s own repair mechanisms to heal previously irreparable tissues or organs. As this initial concept has evolved, regenerative medicine can be thought of as encompassing several related disciplines. One of the earliest references to the concept of regenerative medicine is found in a 1992 article on hospital administration, in a series of short paragraphs on future technologies that would impact hospitals and medical care: “A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems” ( 1).
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