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New insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis: a potential role for stem cells in the lung parenchyma and implications for therapy.
Pharm Res 2007; 24(5):819-41PR

Abstract

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal form of interstitial lung disease. It is characterized by injury with loss of lung epithelial cells and abnormal tissue repair, resulting in replacement of normal functional tissue, abnormal accumulation of fibroblasts and myofibroblasts, deposition of extracellular matrix, and distortion of lung architecture which results in respiratory failure. Despite improvements in the diagnostic approach to IPF and active research in recent years, the molecular mechanisms of the disease remain poorly understood. This highly lethal lung disorder continues to pose major clinical challenges since an effective therapeutic regimen has yet to be identified and developed. For example, a treatment modality has been based on the assumption that IPF is a chronic inflammatory disease, yet most available anti-inflammatory drugs are not effective in treating it. Hence researchers are now focusing on understanding alternative underlying mechanisms involved in the pathogenesis of IPF in the hope of discovering potentially new pharmaceutical targets. This paper will focus on lung tissue repair, regeneration, remodeling, and cell types that may be important to consider in therapeutic interventions and includes a more detailed discussion of the potential targets of current therapeutic attack in pulmonary fibrosis. The discovery that adult bone marrow stem cells can contribute to the formation of differentiated cell types in other tissues, especially after injury, implies that they have the potential to participate in tissue remodeling, and perhaps regeneration. The current promise of the use of adult stem cells for tissue regeneration, and the belief that once irreversibly damaged tissue could be restored to a normal functional capacity using stem cell-based therapy, suggests a novel approach for treatment of diverse chronic diseases. However this optimism is tempered by current evidence that the pathogenesis of pulmonary fibrosis may involve the recruitment of bone marrow-derived fibroblasts, which are the key contributors to the pathogenesis of this chronic progressive disorder. Nevertheless, stem cell-related therapies are widely viewed as promising treatment options for patients suffering from various types of pulmonary diseases. Gender mismatched bone marrow or lung transplant recipients serve as natural populations in which to study the role of bone marrow-derived stem cells in recovery from pulmonary diseases. Understanding the mechanism of recruitment of stem cells to sites of injury, and their involvement in tissue repair, regeneration, and remodeling may offer a novel therapeutic target for developing more effective treatments against this fatal disorder. This article reviews the new concepts in the pathogenesis, current and future treatment options of pulmonary fibrosis, and the recent advances regarding the roles of stem cells in lung tissue repair, regeneration, and remodeling.

Authors+Show Affiliations

Division of Pulmonary Medicine & Critical Care, Department of Internal Medicine, University of Michigan Medical School, 2215 Fuller Rd. VAMC 11R, Ann Arbor, Michigan 48105, USA. nazy@umich.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Review

Language

eng

PubMed ID

17333393

Citation

Gharaee-Kermani, Mehrnaz, et al. "New Insights Into the Pathogenesis and Treatment of Idiopathic Pulmonary Fibrosis: a Potential Role for Stem Cells in the Lung Parenchyma and Implications for Therapy." Pharmaceutical Research, vol. 24, no. 5, 2007, pp. 819-41.
Gharaee-Kermani M, Gyetko MR, Hu B, et al. New insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis: a potential role for stem cells in the lung parenchyma and implications for therapy. Pharm Res. 2007;24(5):819-41.
Gharaee-Kermani, M., Gyetko, M. R., Hu, B., & Phan, S. H. (2007). New insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis: a potential role for stem cells in the lung parenchyma and implications for therapy. Pharmaceutical Research, 24(5), pp. 819-41.
Gharaee-Kermani M, et al. New Insights Into the Pathogenesis and Treatment of Idiopathic Pulmonary Fibrosis: a Potential Role for Stem Cells in the Lung Parenchyma and Implications for Therapy. Pharm Res. 2007;24(5):819-41. PubMed PMID: 17333393.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis: a potential role for stem cells in the lung parenchyma and implications for therapy. AU - Gharaee-Kermani,Mehrnaz, AU - Gyetko,Margaret R, AU - Hu,Biao, AU - Phan,Sem H, Y1 - 2007/03/01/ PY - 2006/09/29/received PY - 2006/12/13/accepted PY - 2007/3/3/pubmed PY - 2007/10/18/medline PY - 2007/3/3/entrez SP - 819 EP - 41 JF - Pharmaceutical research JO - Pharm. Res. VL - 24 IS - 5 N2 - Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal form of interstitial lung disease. It is characterized by injury with loss of lung epithelial cells and abnormal tissue repair, resulting in replacement of normal functional tissue, abnormal accumulation of fibroblasts and myofibroblasts, deposition of extracellular matrix, and distortion of lung architecture which results in respiratory failure. Despite improvements in the diagnostic approach to IPF and active research in recent years, the molecular mechanisms of the disease remain poorly understood. This highly lethal lung disorder continues to pose major clinical challenges since an effective therapeutic regimen has yet to be identified and developed. For example, a treatment modality has been based on the assumption that IPF is a chronic inflammatory disease, yet most available anti-inflammatory drugs are not effective in treating it. Hence researchers are now focusing on understanding alternative underlying mechanisms involved in the pathogenesis of IPF in the hope of discovering potentially new pharmaceutical targets. This paper will focus on lung tissue repair, regeneration, remodeling, and cell types that may be important to consider in therapeutic interventions and includes a more detailed discussion of the potential targets of current therapeutic attack in pulmonary fibrosis. The discovery that adult bone marrow stem cells can contribute to the formation of differentiated cell types in other tissues, especially after injury, implies that they have the potential to participate in tissue remodeling, and perhaps regeneration. The current promise of the use of adult stem cells for tissue regeneration, and the belief that once irreversibly damaged tissue could be restored to a normal functional capacity using stem cell-based therapy, suggests a novel approach for treatment of diverse chronic diseases. However this optimism is tempered by current evidence that the pathogenesis of pulmonary fibrosis may involve the recruitment of bone marrow-derived fibroblasts, which are the key contributors to the pathogenesis of this chronic progressive disorder. Nevertheless, stem cell-related therapies are widely viewed as promising treatment options for patients suffering from various types of pulmonary diseases. Gender mismatched bone marrow or lung transplant recipients serve as natural populations in which to study the role of bone marrow-derived stem cells in recovery from pulmonary diseases. Understanding the mechanism of recruitment of stem cells to sites of injury, and their involvement in tissue repair, regeneration, and remodeling may offer a novel therapeutic target for developing more effective treatments against this fatal disorder. This article reviews the new concepts in the pathogenesis, current and future treatment options of pulmonary fibrosis, and the recent advances regarding the roles of stem cells in lung tissue repair, regeneration, and remodeling. SN - 0724-8741 UR - https://www.unboundmedicine.com/medline/citation/17333393/New_insights_into_the_pathogenesis_and_treatment_of_idiopathic_pulmonary_fibrosis:_a_potential_role_for_stem_cells_in_the_lung_parenchyma_and_implications_for_therapy_ L2 - https://doi.org/10.1007/s11095-006-9216-x DB - PRIME DP - Unbound Medicine ER -