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Human lung stem cells: oh, the places you'll go!

Königshoff M, Schwarz J, Eickelberg O - EMBO Mol Med (2011)

View Article: PubMed Central - PubMed

Affiliation: Comprehensive Pneumology Center, Ludwig-Maximilians-University, University Hospital Grosshadern, Munich, Germany.

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See related article in The New England Journal of Medicine http://dx.doi.org/10.1056/NEJMoa1101324 Chronic lung diseases (CLD), including chronic obstructive pulmonary disease (COPD), asthma, lung cancer, interstitial lung disease or pulmonary hypertension, are the second leading cause of death worldwide and a significant global health problem... Only limited effective causal therapies have been developed thus far for CLD, as such, lung transplantation remains the only available therapeutic option with the potential of long-term survival for most patients with end-stage CLD... Future studies will now need to address the specificity of these niches, the characteristics of their microenvironment and whether these cells also may circulate (Montani et al, )... While Kajstura et al have provided compelling evidence for the origin of resident stem cells in human lungs, the definitive conclusions of this study are exciting yet limiting and replication of the most significant observations in a second, independent group of subjects is now required... Moreover, the findings thus far will clearly benefit from the therapeutic application of human lung stem cells into animal models more closely mimicking human CLD, such as lung fibrosis or COPD... If so, the underlying molecular mechanisms promoting cellular replacement and regeneration by lung stem cells is still undefined and will give a multitude of further questions for future studies... This study contains a number of additional interesting aspects: First, the findings that neither cardiac stem cells nor haematopoietic stem cells, which exhibit similar stem cell characteristics, failed to repair lung injury demands attention... Further, cells derived from bone marrow or peripheral blood, such as haematopoietic stem cells, mesenchymal stem cells or endothelial progenitor cells harbour the benefit of autologous transplantation and lack of immunogenicity, but mostly require ex vivo expansion or are limited in the supply of the adequate cell population... Therefore, resident adult lung stem cells, in comparison to non-resident stem cells, may have the potential to provide lung-specific matched stem cells with promising capacity of exogenous, as well as endogenous, in vivo differentiation for cell replacement therapies. »These findings manifest an exciting field for further research. « In conclusion, Kajstura et al convincingly reported the existence of resident human adult lung stem cells and that these are a potential source for regenerative medicine in the lung (Fig 1)... Which stimuli are needed to activate possible niches to induce endogenous repair and regenerative processes of the adult diseased lung? At this point, we also do not know whether these cells may turn to places where they should not be found... Lung progenitor cells have been suggested to be involved in cancer development, as such it is reasonable to argue that cancer stem cells may originate from resident lung stem cells, thereby, driving lung cancer formation (Giangreco et al, )... Cell-specific targeting of injured, de-differentiated or malignant cells, that provide critical functions in disease initiation and progression, would provide further therapeutic options... In light of the devastating course of CLD, the goal to (do nothing less but) rebuild the diseased human lung is ambitious, but also imperative.

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Human lung stem cells in CLD progression and therapy. Multipotent resident lung stem cells (green) originate from a variety of compartments and may contribute to the progression of several CLD. On the other hand, adult human lung stem cells could be used to exploit different therapeutic options.
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fig01: Human lung stem cells in CLD progression and therapy. Multipotent resident lung stem cells (green) originate from a variety of compartments and may contribute to the progression of several CLD. On the other hand, adult human lung stem cells could be used to exploit different therapeutic options.

Mentions: In conclusion, Kajstura et al convincingly reported the existence of resident human adult lung stem cells and that these are a potential source for regenerative medicine in the lung (Fig 1). These findings manifest an exciting field for further research. Clearly, the question whether these cell populations or their functions are altered in CLD and how these cells change in different diseases in terms of numbers, markers or location now define exciting areas of research. If these cells are capable of repairing or regenerating injured lung tissue, why does this not at all happen endogenously in CLD or only to a very limited extent? Which stimuli are needed to activate possible niches to induce endogenous repair and regenerative processes of the adult diseased lung? At this point, we also do not know whether these cells may turn to places where they should not be found. To elucidate if the stem cell population of Kajstura et al is involved in initiation and progression of CLD, further studies are clearly required. In addition, inappropriate restore mechanisms, improper terminal differentiation or apoptosis of lung stem cells may be a reason for pathology of CLD.


Human lung stem cells: oh, the places you'll go!

Königshoff M, Schwarz J, Eickelberg O - EMBO Mol Med (2011)

Human lung stem cells in CLD progression and therapy. Multipotent resident lung stem cells (green) originate from a variety of compartments and may contribute to the progression of several CLD. On the other hand, adult human lung stem cells could be used to exploit different therapeutic options.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3377101&req=5

fig01: Human lung stem cells in CLD progression and therapy. Multipotent resident lung stem cells (green) originate from a variety of compartments and may contribute to the progression of several CLD. On the other hand, adult human lung stem cells could be used to exploit different therapeutic options.
Mentions: In conclusion, Kajstura et al convincingly reported the existence of resident human adult lung stem cells and that these are a potential source for regenerative medicine in the lung (Fig 1). These findings manifest an exciting field for further research. Clearly, the question whether these cell populations or their functions are altered in CLD and how these cells change in different diseases in terms of numbers, markers or location now define exciting areas of research. If these cells are capable of repairing or regenerating injured lung tissue, why does this not at all happen endogenously in CLD or only to a very limited extent? Which stimuli are needed to activate possible niches to induce endogenous repair and regenerative processes of the adult diseased lung? At this point, we also do not know whether these cells may turn to places where they should not be found. To elucidate if the stem cell population of Kajstura et al is involved in initiation and progression of CLD, further studies are clearly required. In addition, inappropriate restore mechanisms, improper terminal differentiation or apoptosis of lung stem cells may be a reason for pathology of CLD.

View Article: PubMed Central - PubMed

Affiliation: Comprehensive Pneumology Center, Ludwig-Maximilians-University, University Hospital Grosshadern, Munich, Germany.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

See related article in The New England Journal of Medicine http://dx.doi.org/10.1056/NEJMoa1101324 Chronic lung diseases (CLD), including chronic obstructive pulmonary disease (COPD), asthma, lung cancer, interstitial lung disease or pulmonary hypertension, are the second leading cause of death worldwide and a significant global health problem... Only limited effective causal therapies have been developed thus far for CLD, as such, lung transplantation remains the only available therapeutic option with the potential of long-term survival for most patients with end-stage CLD... Future studies will now need to address the specificity of these niches, the characteristics of their microenvironment and whether these cells also may circulate (Montani et al, )... While Kajstura et al have provided compelling evidence for the origin of resident stem cells in human lungs, the definitive conclusions of this study are exciting yet limiting and replication of the most significant observations in a second, independent group of subjects is now required... Moreover, the findings thus far will clearly benefit from the therapeutic application of human lung stem cells into animal models more closely mimicking human CLD, such as lung fibrosis or COPD... If so, the underlying molecular mechanisms promoting cellular replacement and regeneration by lung stem cells is still undefined and will give a multitude of further questions for future studies... This study contains a number of additional interesting aspects: First, the findings that neither cardiac stem cells nor haematopoietic stem cells, which exhibit similar stem cell characteristics, failed to repair lung injury demands attention... Further, cells derived from bone marrow or peripheral blood, such as haematopoietic stem cells, mesenchymal stem cells or endothelial progenitor cells harbour the benefit of autologous transplantation and lack of immunogenicity, but mostly require ex vivo expansion or are limited in the supply of the adequate cell population... Therefore, resident adult lung stem cells, in comparison to non-resident stem cells, may have the potential to provide lung-specific matched stem cells with promising capacity of exogenous, as well as endogenous, in vivo differentiation for cell replacement therapies. »These findings manifest an exciting field for further research. « In conclusion, Kajstura et al convincingly reported the existence of resident human adult lung stem cells and that these are a potential source for regenerative medicine in the lung (Fig 1)... Which stimuli are needed to activate possible niches to induce endogenous repair and regenerative processes of the adult diseased lung? At this point, we also do not know whether these cells may turn to places where they should not be found... Lung progenitor cells have been suggested to be involved in cancer development, as such it is reasonable to argue that cancer stem cells may originate from resident lung stem cells, thereby, driving lung cancer formation (Giangreco et al, )... Cell-specific targeting of injured, de-differentiated or malignant cells, that provide critical functions in disease initiation and progression, would provide further therapeutic options... In light of the devastating course of CLD, the goal to (do nothing less but) rebuild the diseased human lung is ambitious, but also imperative.

No MeSH data available.


Related in: MedlinePlus