Adult Bone Marrow-Derived Stem Cells for the Lung: Implications for Pediatric Lung Diseases

Haaften, Timothy van; Thébaud, Bernard

doi:10.1203/01.pdr.0000203550.50258.5a

Cited by 30 publications

(14 citation statements)

References 52 publications

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“…ES cells are pluripotent cells and are derived from the inner cell mass of the blastocyst stage of embryos (30). They are able to form any cell type and tissue in the animal body and therefore have great therapeutic capacity to regenerate any damaged tissue (23). ES cells isolated from the inner cell mass of a blastocyst can be characterized in vivo by the formation of chimeric embryos when injected into an immunocompromised host, and by differentiation in vitro to form embryoid bodies (31).…”

Section: Stem Cells Definition and Backgroundmentioning

confidence: 99%

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

Gharaee−Kermani

Gyetko

et al. 2007

Pharm Res

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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.

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Section: Stem Cells Definition and Backgroundmentioning

confidence: 99%

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

Gharaee−Kermani

Gyetko

et al. 2007

Pharm Res

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“…Arrest of such tissue maturation process may induce conditions like bronchopulmonary dysplasia (BPD) [4], which is characterized by the arrest in alveolar growth in premature infants, causing neonatal respiratory distress syndrome. Recently it had been suggested that the involvement of such cells potentially play important roles in the recovery process of certain diseases such severe acute respiratory syndrome (SARS).…”

Section: The Roles Of Stem/progenitor Cells In Lung Growth and Repairmentioning

confidence: 99%

“…The goal of stem cell therapy is to therapeutically deliver to the damaged organs stem/progenitor cells to augment the regenerative capacity of the damaged tissue, thus preserving its function. The experimental pulmonary disease models which have been studied to date include acute respiratory distress syndrome [6,13], chronic lung diseases of pre-maturity [4], compensatory pulmonary hyperplasia following lung resections [14], bronchiolitis obliterans [3], cystic fibrosis [15,16], emphysema [17][18][19][20], idiopathic pulmonary hypertension [21][22][23][24][25] and pulmonary fibrosis [26]. The majority of these studies are very preliminary and far premature from clinical trials and therapeutic use.…”

Section: Regenerative Therapy By Stem/prog-enitor Cell Transplantationmentioning

confidence: 99%

Cell Therapy for Respiratory Diseases: Optimizing Cell Delivery Strategies

Karoubi¹,

Courtman²,

Chiu

2007

CRMR

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Cell therapy is a new research approach being vigorously pursued for the treatment of patients who suffer from many respiratory diseases, ranging from acute respiratory distress syndrome (ARDS), emphysema to idiopathic pulmonary hypertension etc. In such studies, stem cells or progenitor cells are administered with the goal to regenerate damaged pulmonary tissues and to improve their functions. Various adult and embryo derived stem cells are being employed for such investigations. However, as the first crucial step for this approach to be successful, cell delivery methods need to be optimized such that the cells can not only reach the target organs but also can be retained in sufficient quantities.The optimal strategy for cell delivery will depend on the anatomical and functional characteristics of the target organs. For example, for solid organs such as the brain (e.g. for Parkinson's disease) or the heart (for myocardial infarction), direct injection of the cells is being employed, although for the latter, powerful myocardial contractions could cause massive mechanical cell loss from the cell implant sites. For the islet cell transplants (for diabetes), intrahepatic implantation via portal vein appears convenient and effective. As the lung is neither a solid nor an endocrine organ, cell delivery via vascular route appears mandatory.It is now well established that many marrow derived stem / progenitor cells, such as the endothelial progenitor cells (EPCs), are capable of homing in to the tissues suffering from acute injuries (e.g. the lung with ARDS). The roles of inflammatory cytokines and endothelial adhesion molecules for such homing mechanism are being elucidated. Thus for patients suffering from acute lung injuries, intravenous administration of donor cells could be an effective method of cell delivery. However, in patients with chronic conditions such as emphysema, pulmonary fibrosis or hypertension, intravascular delivery of cells results in minimal cell retention, as the donor cells will pass through the pulmonary circulation readily.In this review, we will examine a number of respiratory diseases for which stem cell therapy is being studied, then focusing on the strategies to enable the "trapping" of donor cells administered into the pulmonary circulation in lungs without acute injuries. They may include the pre-treatment of the pulmonary capillary endothelium to induce the expression of adhesion molecules, and more recently the use of innovatively engineered biodegradable microcapsules which can enhance intravascular cell retention and survival. Successful strategies to deliver donor cells to the lung will enable us to rigorously examine the efficacy of cell therapy, thus potentially benefit vast population of patients who suffer wide varieties of respiratory diseases.

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“…Additional evidence for lung engraftment following bone marrow or lung transplantation comes from biopsies of human lung [16][17][18][19]. Other aspects of adult stem cell biology in lung disease have been thoroughly reviewed recently [20,21].…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow-Derived Cells Participate in Stromal Remodeling of the Lung Following Acute Bacterial Pneumonia in Mice

Serikov

Mikhaylov

Krasnodembskay

et al. 2008

Lung

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Bone marrow-derived cells (BMDC) have been shown to graft injured tissues, differentiate in specialized cells, and participate in repair. The importance of these processes in acute lung bacterial inflammation and development of fibrosis is unknown. The goal of this study was to investigate the temporal sequence and lineage commitment of BMDC in mouse lungs injured by bacterial pneumonia. We transplanted GFP-tagged BMDC into 5-Gy-irradiated C57BL/6 mice. After 3 months of recovery, mice were subjected to LD 50 intratracheal instillation of live E. coli (controls received saline) which produced pneumonia and subsequent areas of fibrosis. Lungs were investigated by immunohistology for up to 6 months. At the peak of lung inflammation, the predominant influx of BMDC were GFP + leukocytes. Postinflammatory foci of lung fibrosis were evident after 1-2 months. The fibrotic foci in lung stroma contained clusters of GFP + CD45 + cells, GFP + vimentin-positive cells, and GFP + collagen I-positive fibroblasts. GFP + endothelial or epithelial cells were not identified. These data suggest that following 5-Gy irradiation and acute bacterial pneumonia, BMDC may temporarily participate in lung postinflammatory repair and stromal remodeling without long-term engraftment as specialized endothelial or epithelial cells.

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Adult Bone Marrow-Derived Stem Cells for the Lung: Implications for Pediatric Lung Diseases

Cited by 30 publications

References 52 publications

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

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

Cell Therapy for Respiratory Diseases: Optimizing Cell Delivery Strategies

Bone Marrow-Derived Cells Participate in Stromal Remodeling of the Lung Following Acute Bacterial Pneumonia in Mice

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