Persistent vascular defects in lung allografts attributed to defective endogenous endothelial progenitors

Chinoy, Mala R.; Miller, Sue Ann; Myers, Roland L.; Cilley, Robert E.; Dillon, Peter W.

doi:10.1016/j.jss.2004.09.022

Cited by 6 publications

(3 citation statements)

References 18 publications

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“…Moreover, a number of data indicate that alterations of the pulmonary vasculature may depend upon reduced or defective marrow-derived progenitor cells. [3][4][5][6][7] Therefore, when MF develops in patients with PH, it may be suggested that the increase in peripheral CD34 ϩ cells is masked by the reduced CD34 ϩ cell count that is observed at basal conditions in these subjects. This may explain why the authors found no difference in CD34 ϩ cells between patients with PH-induced MF and control subjects.…”

Section: To the Editormentioning

confidence: 99%

Circulating CD34+ cells, pulmonary hypertension, and myelofibrosis

Fadini

Schiavon²,

Cantini³

et al. 2006

Blood

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Response:Deferasirox (ICL670) effectively reduces liver iron concentration, whether assessed by biopsy or SQUIDWe thank Drs Fischer, Harmatz, and Nielsen for their letter and interest in our paper. In this study, liver iron concentration (LIC) was assessed either by biopsy (84% of patients) or superconducting quantum interference device (SQUID; 16%, primarily children and adults with contraindications to biopsy). SQUID assessments were performed at 3 centers (in Italy, Germany, and the US); baseline and end-of-study assessments were always conducted at the same site. We acknowledge that the discrepancy between LIC values obtained from biopsy and SQUID was primarily due to the accepted conversion factor of 3.33 that was used to convert wet-weight into dry-weight values. 1 As discussed in the paper, we opted to present prenormalized LIC values because the discrepancy between values obtained from biopsy and SQUID was only identified late in the trial via a validation study. By this time, most patients had been assigned doses according to baseline LIC and most had completed a large proportion of the study. Subsequently, the more appropriate correction factor noted by Drs Fischer, Harmatz, and Nielsen (5.83 Ϯ 0.60) was determined through an independent study. 2 The effect of deferasirox for reducing iron burden, as measured by LIC, was potentially underreported in our paper because we elected to use prenormalized SQUID data. Although these values are different in absolute magnitude from the prenormalized values, they do not differ in the relative magnitude of response. The inclusion or exclusion of patients whose LIC was assessed by SQUID does not alter the primary outcome of the study, which was to demonstrate that deferasirox is generally well tolerated and effective for reducing body iron burden.Despite the technical limitations of the application in this study, SQUID has made, and is continuing to make, important contributions to the field of iron chelation research. As with all methods that are used in longitudinal assessments, consistency of technique is of utmost importance. For the patients who have access, SQUID will remain an important tool to monitor iron overload and response to chelation therapy. Maria Domenica Cappellini

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Section: To the Editormentioning

confidence: 99%

Circulating CD34+ cells, pulmonary hypertension, and myelofibrosis

Fadini

Schiavon²,

Cantini³

et al. 2006

Blood

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“…Whole fetal mouse lung has been allografted subcutaneously into immunodeficient mice by Schwarz et al [39] and Chinoy et al [40]. However, it takes up to 14 days for the E14.5 lung rudiments to reach the early saccular stage.…”

Section: Discussionmentioning

confidence: 99%

Impaired Elastin Deposition in Fstl1−/− Lung Allograft under the Renal Capsule

Geng

Dong

et al. 2013

PLoS ONE

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Lung alveolar development in late gestation is a process important to postnatal survival. Follistatin-like 1 (Fstl1) is a matricellular protein of the Bmp antagonist class, which is involved in the differentiation/maturation of alveolar epithelial cells during saccular stage of lung development. This study investigates the role of Fstl1 on elastin deposition in mesenchyme and subsequent secondary septation in the late gestation stage of terminal saccular formation. To this aim, we modified the renal capsule allograft model for lung organ culture by grafting diced E15.5 distal lung underneath the renal capsule of syngeneic host and cultured up to 7 days. The saccular development of the diced lung allografts, as indicated by the morphology, epithelial and vascular developments, occurred in a manner similar to that in utero. Fstl1 deficiency caused atelectatic phenotype companied by impaired epithelial differentiation in D3 Fstl1−/− lung allografts, which is similar to that of E18.5 Fstl1−/− lungs, supporting the role of Fstl1 during saccular stage. Inhibition of Bmp signaling by intraperitoneal injection of dorsomorphin in the host mice rescued the pulmonary atelectasis of D3 Fstl1−/− allografts. Furthermore, a marked reduction in elastin expression and deposition was observed in walls of air sacs of E18.5 Fstl1−/− lungs and at the tips of the developing alveolar septae of D7 Fstl1−/− allografts. Thus, in addition to its role on alveolar epithelium, Fstl1 is crucial for elastin expression and deposition in mesenchyme during lung alveologenesis. Our data demonstrates that the modified renal capsule allograft model for lung organ culture is a robust and efficient technique to increase our understanding of saccular stage of lung development.

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“…These studies suggest that disrupted vascularization was involved in the pathophysiology of pulmonary hypoplasia in CDH. However, few studies have investigated the role of EPCs and SDF1 signaling in pulmonary hypoplasia in CDH (9,17).…”

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confidence: 99%

Cord blood-derived endothelial colony-forming cell function is disrupted in congenital diaphragmatic hernia

Fujinaga

Watanabe

Kato

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Vascular growth is necessary for normal lung development. Although endothelial progenitor cells (EPCs) play an important role in vascularization, little is known about EPC function in congenital diaphragmatic hernia (CDH), a severe neonatal condition that is associated with pulmonary hypoplasia. We hypothesized that the function of endothelial colony-forming cells (ECFCs), a type of EPC, is impaired in CDH. Cord blood (CB) was collected from full-term CDH patients and healthy controls. We assessed CB progenitor cell populations as well as plasma vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1α (SDF1α) levels. CB ECFC clonogenicity; growth kinetics; migration; production of VEGF, SDF1α, and nitric oxide (NO); vasculogenic capacity; and mRNA expression of VEGF-A, fms-related tyrosine kinase 1 (FLT1), kinase insert domain receptor (KDR), nitric oxide synthase (NOS) 1-3, SDF1, and chemokine (C-X-C motif) receptor 4 (CXCR4) were also assessed. Compared with controls, CB ECFCs were decreased in CDH. CDH ECFCs had reduced potential for self-renewal, clonogenicity, proliferation, and migration. Their capacity for NO production was enhanced but their response to VEGF was blunted in CDH ECFCs. In vivo potential for de novo vasculogenesis was reduced in CDH ECFCs. There was no difference in CB plasma VEGF and SDF1α concentrations, VEGF and SDF1α production by ECFCs, and ECFC mRNA expression of VEGF-A, FLT1, KDR, NOS1-3, SDF1, and CXCR4 between CDH and control subjects. In conclusion, CB ECFC function is disrupted in CDH, but these changes may be caused by mechanisms other than alteration of VEGF-NO and SDF1-CXCR4 signaling.

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Persistent vascular defects in lung allografts attributed to defective endogenous endothelial progenitors

Cited by 6 publications

References 18 publications

Circulating CD34+ cells, pulmonary hypertension, and myelofibrosis

Circulating CD34+ cells, pulmonary hypertension, and myelofibrosis

Impaired Elastin Deposition in Fstl1−/− Lung Allograft under the Renal Capsule

Cord blood-derived endothelial colony-forming cell function is disrupted in congenital diaphragmatic hernia

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