CD34<sup>+</sup> Progenitor to Endothelial Cell Transition in Post-Pneumonectomy Angiogenesis

Chamoto, Kenji; Gibney, Barry C.; Lee, Grace S.; Miao, Lin; Collings-Simpson, Dinee; Voswinckel, Robert; Konerding, Moritz A.; Tsuda, Akira; Mentzer, Steven J.

doi:10.1165/rcmb.2011-0249oc

Cited by 35 publications

(39 citation statements)

References 48 publications

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“…The mechanism responsible for this structural damping is unclear, but likely reflects components intimately involved in tissue regeneration including proliferating cells, extracellular connective tissue and the alveolar air-liquid interface [28, 29]. Consistent with this interpretation, our data demonstrated a significant change in tissue damping coincident with the maximal growth phase; that is, the phase of lung growth associated with cellular proliferation and gene transcription [12-14]. We speculate that the return to baseline G and H was a reflection of neoalveolarization.…”

Section: Discussionsupporting

confidence: 75%

“…Recent studies of post-pneumonectomy lung cells [12], including endothelial cells [13, 14] and alveolar macrophages [15], have demonstrated an unexpected transcriptional time course; that is, gene transcription and cell proliferation that are minimal at 3 days, but peak 6 to 7 days after pneumonectomy. Distinct from the stretch responses studied in vitro—typically detected within hours of the stretch signal—these results indicate that post-pneumonectomy mechanics may not be optimally characterized as an immediate one-time stretch signal, but rather as dynamic anatomical and mechanical adaptations to the post-pneumonectomy thorax that occur over days to weeks.…”

Section: Introductionmentioning

confidence: 99%

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Mechanostructural adaptations preceding postpneumonectomy lung growth

Gibney¹,

Houdek²,

Chamoto³

et al. 2012

Experimental Lung Research

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In many species, pneumonectomy results in compensatory growth in the remaining lung. Although the late mechanical consequences of murine pneumonectomy are known, little is known about the anatomic adaptations and respiratory mechanics during compensatory lung growth. To investigate the structural and mechanical changes during compensatory growth, mice were studied for 21 days after left pneumonectomy using microCT and respiratory system impedance (FlexiVent). Anatomic changes after left pneumonectomy included minimal mediastinal shift or chestwall remodeling, but significant displacement of the heart and cardiac lobe. Mean displacement of the cardiac lobe centroid was 5.2±0.8mm. Lung impedance measurements were used to investigate the associated changes in respiratory mechanics. Quasi-static pressure-volume loops demonstrated progressive increase in volumes with decreased distensibility. Measures of quasi-static compliance and elastance were increased at all time points post pneumonectomy (p < 0.01). Oscillatory mechanics demonstrated a significant change in tissue impedance on the 3rd day after pneumonectomy. The input impedance on day 3 after pneumonectomy demonstrated a significant increase in tissue damping (5.8 versus 4.3 cmH2O/ml) and elastance (36.7 versus 26.6 cmH2O/ml) when compared to controls. At all points, hysteresivity was unchanged (0.17). We conclude that the timing and duration of the mechanical changes was consistent with a mechanical signal for compensatory growth.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Mechanostructural adaptations preceding postpneumonectomy lung growth

Gibney¹,

Houdek²,

Chamoto³

et al. 2012

Experimental Lung Research

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“…Most importantly, parabiosis provides a fate map of cell migration without bone marrow transplantation or ex vivo labeling. Using the parabiosis model we have demonstrated dramatic numbers of EPCs migrating to, and integrating into, the vascular endothelium of the growing mouse lung (66). …”

Section: Pillar Extensionmentioning

confidence: 99%

Intussusceptive angiogenesis: expansion and remodeling of microvascular networks

2014

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Intussusceptive angiogenesis is a dynamic intravascular process capable of dramatically modifying the structure of the microcirculation. The distinctive structural feature of intussusceptive angiogenesis is the intussusceptive pillar—a cylindrical microstructure that spans the lumen of small vessels and capillaries. The extension of the intussusceptive pillar appears to be a mechanism for pruning redundant or inefficient vessels, modifying the branch angle of bifurcating vessels and duplicating existing vessels. Despite the biological importance and therapeutic potential, intussusceptive angiogenesis remains a mystery, in part, because it is an intravascular process that is unseen by conventional light microscopy. Here, we review several fundamental questions in the context of our current understanding of both intussusceptive and sprouting angiogenesis. 1) What are the physiologic signals that trigger pillar formation? 2) What endothelial and blood flow conditions specify pillar location? 3) How do pillars respond to the mechanical influence of blood flow? 4) What biological influences contribute to pillar extension? The answers to these questions are likely to provide important insights into the structure and function of microvascular networks.

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“…First, studies in both humans and rodents have demonstrated the importance of macrophages in maintaining the hematopoietic stem cell niche (Ehninger and Trumpp, 2011). The recent finding that blood-borne CD34 + progenitor cells contribute to compensatory lung growth (Chamoto et al, 2011) suggests that alveolar macrophages may participate in regulating alveolar construction. Second, tissue macrophages have been shown to regulate epithelial proliferation (Cakarova et al, 2009) as well as neovascularization and vascular stabilization (Sunderkotter et al, 1994) Both epithelial proliferation and alveolar angiogenesis are central features of post-pneumonectomy lung growth.…”

Section: Introductionmentioning

confidence: 99%

Alveolar macrophage dynamics in murine lung regeneration

Chamoto¹,

Gibney²,

Ackermann³

et al. 2012

Journal Cellular Physiology

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In most mammalian species, the removal of one lung results in dramatic compensatory growth of the remaining lung. To investigate the contribution of alveolar macrophages (AM) to murine post-pneumonectomy lung growth, we studied bronchoalveolar lavage (BAL)-derived AM on 3, 7, 14 and 21 days after left pneumonectomy. BAL demonstrated a 3.0-fold increase in AM (CD45+, CD11b−, CD11c+, F4/80+, Gr-1− ) by 14 days after pneumonectomy. Cell cycle flow cytometry of the BAL-derived cells demonstrated an increase in S+G2 phase cells on days 3 (11.3± 2.7 %) and 7 (12.1±1.8 %) after pneumonectomy. Correspondingly, AM demonstrated increased expression of VEGFR1 and MHC class II between days 3 and 14 after pneumonectomy. To investigate the potential contribution of peripheral blood cells to this AM population, parabiotic mice (wild-type/GFP) underwent left pneumonectomy. Analysis of GFP+ cells in the post-pneumonectomy lung demonstrated that by day 14, less than 1% of the alveolar macrophage population were derived from the peripheral blood. Finally, AM gene transcription demonstrated a significant shift from decreased transcription of angiogenesis-related genes on day 3 to increased transcription on day 7 after pneumonectomy. The increased number of locally proliferating AM, combined with their growth-related gene transcription, suggests that AM actively participate in compensatory lung growth.

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CD34⁺ Progenitor to Endothelial Cell Transition in Post-Pneumonectomy Angiogenesis

Cited by 35 publications

References 48 publications

Mechanostructural adaptations preceding postpneumonectomy lung growth

Mechanostructural adaptations preceding postpneumonectomy lung growth

Intussusceptive angiogenesis: expansion and remodeling of microvascular networks

Alveolar macrophage dynamics in murine lung regeneration

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CD34+ Progenitor to Endothelial Cell Transition in Post-Pneumonectomy Angiogenesis

Cited by 35 publications

References 48 publications

Mechanostructural adaptations preceding postpneumonectomy lung growth

Mechanostructural adaptations preceding postpneumonectomy lung growth

Intussusceptive angiogenesis: expansion and remodeling of microvascular networks

Alveolar macrophage dynamics in murine lung regeneration

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CD34⁺ Progenitor to Endothelial Cell Transition in Post-Pneumonectomy Angiogenesis