Toward Lung Regeneration

New England Journal of Medicine (Impact Factor: 55.87). 05/2011; 364(19):1867-8. DOI: 10.1056/NEJMe1101800
Source: PubMed

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    • "However, the search for human adult lung stem cells has proved a lot more difficult and only minor advancement has been made. Kajstura et al. recently published a controversial study [67,68] claiming the identification of human lung stem cells based on the expression of c-kit [69]. The most surprising finding in this work is the unprecedented identification of cells that can give rise to both endodermal and mesodermal lineages. "
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    ABSTRACT: The isolation and characterization of lung stem and progenitor cells represent an important step towards the understanding of lung repair after injury, lung disease pathogenesis and the identification of the target cells of transformation in lung carcinogenesis. Different approaches using prospective isolation of progenitor cells by flow cytometry or lineage-tracing experiments in mouse models of lung injury have led to the identification of distinct progenitor subpopulations in different morphological regions of the adult lung. Genetically defined mouse models of lung cancer are offering new perspectives on the cells of origin of different subtypes of lung cancer. These mouse models pave the way to further investigate human lung progenitor cells at the origin of lung cancers, as well as to define the nature of the lung cancer stem cells. It will be critical to establish the link between oncogenic driver mutations recently discovered in lung cancers, target cells of transformation and subtypes of lung cancers to enable better stratification of patients for improved therapeutic strategies.
    Full-text · Article · Aug 2012 · Open Biology
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    • "However, in a landmark study Kajstura and colleagues [99] have recently identified a population of c-kit-positive stem cells in the human lung located in the distal lung, the bronchioles and to a lesser extent the alveoli, demonstrating the ability to regenerate all components of an injured mouse lung (Figure 8). This study has generated controversy, particularly in regard to the fact that key experiments lacked appropriate controls, and the fact that, by focusing on human c-kit-positive lung cells, these studies provide only partial insights into the fates of these cells [100,101]. The novelty of these findings is underlined by the fact that multipotent stem cells that can give rise to both endodermal and mesodermal lineages have not previously been described in the lung, nor indeed in any organ. "
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    ABSTRACT: ABSTRACT: A growing understanding of the complexity of the pathophysiology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), coupled with advances in stem cell biology, has led to a renewed interest in the therapeutic potential of stem cells for this devastating disease. Mesenchymal stem cells appear closest to clinical translation, given the evidence that they may favourably modulate the immune response to reduce lung injury, while maintaining host immune-competence and also facilitating lung regeneration and repair. The demonstration that human mesenchymal stem cells exert benefit in the endotoxin-injured human lung is particularly persuasive. Endothelial progenitor cells also demonstrate promise in reducing endothelial damage, which is a key pathophysiological feature of ALI. Embryonic and induced pluripotent stem cells are at an earlier stage in the translational process, but offer the hope of directly replacing injured lung tissue. The lung itself also contains endogenous stem cells, which may ultimately offer the greatest hope for lung diseases, given their physiologic role in replacing and regenerating native lung tissues. However, significant deficits remain in our knowledge regarding the mechanisms of action of stem cells, their efficacy in relevant pre-clinical models, and their safety, particularly in critically ill patients. These gaps need to be addressed before the enormous therapeutic potential of stem cells for ALI/ARDS can be realised.
    Full-text · Article · Mar 2012 · Critical care (London, England)
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    • "The novelty of these findings is underlined by the fact that multipotent stem cells that can give rise to both endodermal and mesodermal lineages have not previously been described in the lung or, indeed, in any organ [9]. Furthermore, there is no known interconversion of endodermal and mesodermal cells during embryonic lung development [18]. "
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    ABSTRACT: The ideal cell type to regenerate an acutely injured or chronically diseased lung would be a stem cell population from the patient's own lung. Consequently, extensive research efforts have focused on identifying and characterizing endogenous lung stem cells. Advances in techniques to facilitate cell isolation, labelling and tracking in vivo to determine their fate have led to the identification of several putative stem cell niches. Recently, convincing evidence has emerged for a novel stem/progenitor cell population in the submucous glands of the cartilaginous airways. These findings support the concept that there is no classical stem cell 'hierarchy' but that different progenitor populations within spatially distinct lung regions regenerate the lung epithelium adjacent to its niche. Intriguingly, recent findings challenge this concept; it was reported that the human lung may contain a primitive stem cell capable of differentiating into multiple cells of both endodermal and mesodermal lineage and of regenerating the injured lung. This suggests that a classical stem cell hierarchy may, in fact, exist in the lung. Although caution is needed in interpreting these emerging findings, the implications for our current concepts regarding lung stem cells, the insights into lung repair and regeneration, and the potential therapeutic implications are considerable.
    Full-text · Article · Oct 2011 · Stem Cell Research & Therapy
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