Ĭhronic obstructive pulmonary disease (COPD) is a respiratory disease that has a major impact worldwide. Sun Z, Li F, Zhou X, Chung KF, Wang W, Wang J. Abstract 1 Stem Cell Therapies for Chronic Obstructive Pulmonary Disease: Current Status of Pre-Clinical Studies and Clinical Trials Note: Abstracts are presented in their original, published format and have not been edited to match JCOPDF style. The other recent papers address some of the questions raised in the review article. The papers presented in this Journal Club include an excellent, comprehensive state of the art review of the studies to date and the important future lines of research. Of course, if that is found to be the case then a major issue will be whether early identification, smoking cessation, adherence to conventional treatments and addressing comorbid conditions may be as or more effective. One of the salient questions is whether these therapies need to be started earlier in less severe stages of the disease process. Intrinsic therapy refers to the delivery of small molecules (retinoid compounds have been the most studied) that can stimulate the endogenous lung stem/progenitor cells to regenerate and replace damaged structures (See Sun et al review paper below).Īs mentioned above, human trials to date have largely failed in showing any benefit but there remain questions about appropriate candidates for such therapy, type of therapy, timing of therapy, dosing issues and a host of other variables that require further study. Extrinsic cell therapy refers to infusing (or endotracheal installation) of stem cells including embryonic stem cells (ESCs), induced pleuripotent stem cells (iPSs), mesenchymal stem cells (MSCs), and human lung stem cells (hLSCs). There has been some work looking at the potential to bioengineer fully intact 3-D lung units that could be transplanted but this is not a likely prospect for the near future. Currently, regenerative therapies are divided into extrinsic therapeutic strategies and intrinsic cell therapy methods. The greatest success has been in acute lung injury models, however. Pre-clinical trials in animal models have suggested regeneration of alveolar-like structures, repair of emphysematous lungs, and reduction of inflammatory responses. Stem cells can differentiate into several different lung cell types such as the alveolar epithelial cells that are destroyed by cigarette smoke leading to emphysematous changes and reduced tethering of small airways causing hyperinflation and gas exchange abnormalities. It is also postulated that by replacing these damaged cells there can be a restoration of normal immune function and a reduction in the inflammatory response to variable exposures such as cigarette smoke, air pollution and airway pathogens in susceptible individuals who develop COPD. With these limitations of standard modalities of therapy, it is attractive to pursue novel regenerative therapies that may be capable of restoring pulmonary function and structures such as airways, terminal bronchioles and alveoli.
Lung transplantation is limited by availability, age restrictions, complications and rejection issues.
Lung volume reduction surgery is reserved often for those with severe disease and has only modest benefits. There has been no definitive evidence that they impact mortality. Indeed, current standard therapies including bronchodilators and inhaled corticosteroids and the phosphodiesterase-4 inhibitor, roflumilast, show modest efficacy at best in reducing exacerbations and improving lung function. Despite this, there remains keen interest in continuing to study so-called “regenerative therapy” for COPD. There have been several phase I clinical trials, mostly looking at safety, and a handful of small phase II clinical trials that essentially have been negative. There are clinics currently offering this therapy, (typically at exorbitant out of pocket cost to the patient), even though there are no phase III randomized controlled trials or Food and Drug Administration approval. Over the last year I have had several patients ask me about stem cell therapy for chronic obstructive pulmonary disease (COPD). Stem cell therapy for COPD: where are we? Chronic Obstr Pulm Dis. Running Head: Journal Club: Stem Cell TherapyĪbbreviations: chronic obstructive pulmonary disease, COPD embryonic stem cells, ESCs induced pleuripotent stem cells, iPSs mesenchymal stem cells, MSCs human lung stem cells, hLSCs adipocyte mesenchymal cells, AD-MSCs bone marrow mesenchymal stem cells, BM-MSCs Wharton’s jelly mesenchymal stem cells, WJ-MSCsĬitation: Balkissoon R.
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