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van der Koog, L.* ; Showell, H.R.D.* ; Nugraha, D.F.* ; Lehmann, M. ; Conlon, T.M. ; Yildirim, A.Ö. ; Fuentes-Mateos, R.* ; Baarsma, H.* ; Ng-Blichfeldt, J.P.* ; Melgert, B.N.* ; Dost, A.F.M.* ; Burgess, J.K.* ; Yam, S.L.S.* ; Heijink, I.H.* ; Ahmed, S.* ; Paschini, M.* ; Jansen, E.M.* ; Hinrichs, W.L.J.* ; Johnson, J.R.* ; Wu, X.* ; Nagelkerke, A.* ; Frijlink, H.W.* ; Kim, C.F.* ; Gosens, R.*

Regenerative therapeutics for chronic obstructive pulmonary disease.

Pharmacol. Rev. 78:100124 (2026)
Publ. Version/Full Text DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases worldwide, characterized by an accelerated loss of lung function. A key problem underlying COPD is increased tissue destruction in combination with defective lung tissue repair. As current therapies do not modify the progression of the disease, new therapies aimed at restoring lung tissue repair in COPD need to be developed. In an attempt to address this major unmet need, there has been a surge in both preclinical and clinical studies, aiming to identify key mechanisms underpinning defective lung repair and the ability to inhibit or even reverse this defect. This includes small molecules such as retinoids, as well as advanced therapy medicinal products such as cell therapies or therapies with cell-derived products such as extracellular vesicles, or secreted proteins. The results of these endeavors have been variable with failures as well as successful proof-of-concepts. In this review, we provide an overview of the current state of the field, including modes of action of the therapeutics that are or have been considered for lung regeneration, including a discussion on the reasons for failure where relevant. In addition, we discuss hurdles in the clinical development of regenerative therapeutics for COPD including clinical outcomes, route of administration and formulation as these are pivotal considerations moving forward. SIGNIFICANCE STATEMENT: Chronic obstructive pulmonary disease is characterized by progressive alveolar destruction and defective epithelial regeneration. Targetable mechanisms, including cellular senescence, altered mesenchymal-epithelial signaling, and chronic inflammation, impair progenitor function and niche integrity. Therapeutic strategies that restore epithelial repair, including small molecules, biologics, and cell-based approaches, represent a promising path toward disease modification and long-term lung function restoration.
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Publication type Article: Journal article
Document type Review
Keywords Keratinocyte Growth-factor; Mesenchymal Stem-cells; Reduces Airway Inflammation; Smoke-induced Emphysema; Protease-antiprotease Imbalance; Copd Pharmacological Trials; Alveolar Epithelial Repair; Induced Lung Inflammation; Activated Receptor-gamma; Genome-wide Association
ISSN (print) / ISBN 0031-6997
e-ISSN 1521-0081
Journal Pharmacological reviews
Quellenangaben Volume: 78, Issue: 3, Pages: , Article Number: 100124 Supplement: ,
Publisher Elsevier
Publishing Place Bethesda, Md.
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
Grants European Commission
UKRI Medical Research Council
Wellcome Trust
Netherlands Organisation for Health Research and Development (ZonMW)
Northern CARA Foundation
Indonesia Endowment Fund for Education (LPDP) of the Ministry of Finance of the Republic of Indonesia, through the Indonesian Education Scholarship (BPI)
Center for Higher Education Funding and Assessment (PPAPT) of the Ministry of Higher Education, Science and Technology
Molecular Life and Health Program of the University of Groningen
Dutch Research Council (NWO)
Lung Foundation Netherlands
German Center for Lung Research (DZL)
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
European Union
European Respiratory Society (ERS)
National Heart Lung Blood Institute
Harvard Stem Cell Institute
Alfred Slifka, Gail and Adam Slifka
Cystic Fibrosis Foundation
UK Biotechnology and Biological Sciences Research Council
UK Medical Research Council
Boehringer Ingelheim