Three-dimensional characteristics of the alveolar capillary network in infant and adult human lungs.
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
23 Sep 2024
23 Sep 2024
Historique:
received:
29
02
2024
accepted:
05
09
2024
revised:
22
07
2024
medline:
24
9
2024
pubmed:
24
9
2024
entrez:
23
9
2024
Statut:
aheadofprint
Résumé
A comprehensive understanding of vascular development in the human lung is still missing. Therefore, samples of infant (n = 5, 26 days to 18 months postnatally) and adult (n = 5, 20 to 40 years) human lungs were subjected to unbiased stereological estimation of the total number of capillary loops. Serial sections were segmented to visualize the alveolar capillary network (ACN) in 3D. The number of capillary loops increased in parallel to lung volume from 26 days to 18 months, while in adults, it was not correlated to lung volume. In infant lungs, two capillary layers were separated by a connective tissue sheet with a growing number of interconnections. In adults, the mature ACN was almost, but not completely, single-layered. Here, the connective tissue was thinner but still centrally positioned, suggesting the persistence of interconnected parts of both layers of the previously double-layered ACN. Small parts of the capillaries remain double-layered and seem to be grouped around the thin connective tissue sheet, suggesting a different mechanism of microvascular maturation than simple fusion of the two layers. These spots are a potential basis for further alveolarization after completion of bulk formation. The 3D data offer a new conceptual approach to microvascular maturation of the lung. Microvascular maturation rather results from reduction than simple fusion of capillary fragments. Adult lungs maintain small double-layered capillary spots. These could offer a potential source of regeneration. The data are important to better understand normal and pathological lung development.
Sections du résumé
BACKGROUND
BACKGROUND
A comprehensive understanding of vascular development in the human lung is still missing.
METHODS
METHODS
Therefore, samples of infant (n = 5, 26 days to 18 months postnatally) and adult (n = 5, 20 to 40 years) human lungs were subjected to unbiased stereological estimation of the total number of capillary loops. Serial sections were segmented to visualize the alveolar capillary network (ACN) in 3D.
RESULTS
RESULTS
The number of capillary loops increased in parallel to lung volume from 26 days to 18 months, while in adults, it was not correlated to lung volume. In infant lungs, two capillary layers were separated by a connective tissue sheet with a growing number of interconnections. In adults, the mature ACN was almost, but not completely, single-layered. Here, the connective tissue was thinner but still centrally positioned, suggesting the persistence of interconnected parts of both layers of the previously double-layered ACN.
CONCLUSIONS
CONCLUSIONS
Small parts of the capillaries remain double-layered and seem to be grouped around the thin connective tissue sheet, suggesting a different mechanism of microvascular maturation than simple fusion of the two layers. These spots are a potential basis for further alveolarization after completion of bulk formation.
IMPACT
CONCLUSIONS
The 3D data offer a new conceptual approach to microvascular maturation of the lung. Microvascular maturation rather results from reduction than simple fusion of capillary fragments. Adult lungs maintain small double-layered capillary spots. These could offer a potential source of regeneration. The data are important to better understand normal and pathological lung development.
Identifiants
pubmed: 39313553
doi: 10.1038/s41390-024-03572-y
pii: 10.1038/s41390-024-03572-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Weibel, E. R. What makes a good lung? Swiss Med. Wkly. 139, 375–386 (2009).
pubmed: 19629765
Burri, P. H. Fetal and postnatal development of the lung. Annu. Rev. Physiol. 46, 617–628 (1984).
pubmed: 6370120
doi: 10.1146/annurev.ph.46.030184.003153
Schittny, J. C. Development of the lung. Cell Tissue Res. 367, 427–444 (2017).
pubmed: 28144783
pmcid: 5320013
doi: 10.1007/s00441-016-2545-0
Burri, P. H. The postnatal growth of the rat lung III. Morphology. Anat. Rec. 180, 77–98 (1974).
pubmed: 4416419
doi: 10.1002/ar.1091800109
Zeltner, T. B. & Burri, P. H. The postnatal development and growth of the human lung. II. morphology. Respir. Physiol. 67, 269–282 (1987).
pubmed: 3575906
doi: 10.1016/0034-5687(87)90058-2
Herring, M. J., Putney, L. F., Wyatt, G., Finkbeiner, W. E. & Hyde, D. M. Growth of alveoli during postnatal development in humans based on stereological estimation. Am. J. Physiol. Lung Cell Mol. Physiol. 307, L338–L344 (2014).
pubmed: 24907055
pmcid: 4137164
doi: 10.1152/ajplung.00094.2014
Tschanz, S. A. et al. Rat lungs show a biphasic formation of new alveoli during postnatal development. J. Appl. Physiol. (1985) 117, 89–95 (2014).
pubmed: 24764134
doi: 10.1152/japplphysiol.01355.2013
Schmid, L., Hyde, D. M. & Schittny, J. C. Microvascular maturation of the septal capillary layers takes place in parallel to alveolarization in human lungs. Am. J. Physiol. Lung Cell Mol. Physiol. 325, L537–L541 (2023).
pubmed: 37605833
pmcid: 11068427
doi: 10.1152/ajplung.00425.2022
Schittny, J. C. How high resolution 3-dimensional imaging changes our understanding of postnatal lung development. Histochem. Cell Biol. 150, 677–691 (2018).
pubmed: 30390117
pmcid: 6267404
doi: 10.1007/s00418-018-1749-7
Mühlfeld, C. et al. Recent developments in 3-D reconstruction and stereology to study the pulmonary vasculature. Am. J. Physiol. Lung Cell Mol. Physiol. 315, L173–L183 (2018).
pubmed: 29644892
doi: 10.1152/ajplung.00541.2017
Haberthür, D. et al. Visualization and stereological characterization of individual rat lung acini by high-resolution X-ray tomographic microscopy. J. Appl. Physiol. (1985) 115, 1379–1387 (2013).
pubmed: 23970533
doi: 10.1152/japplphysiol.00642.2013
Appuhn, S. V. et al. Capillary changes precede disordered alveolarization in a mouse model of bronchopulmonary dysplasia. Am. J. Respir. Cell Mol. Biol. 65, 81–91 (2021).
pubmed: 33784484
doi: 10.1165/rcmb.2021-0004OC
Grothausmann, R., Knudsen, L., Ochs, M. & Mühlfeld, C. Digital 3D reconstructions using histological serial sections of lung tissue including the alveolar capillary network. Am. J. Physiol. Lung Cell Mol. Physiol. 312, L243–L257 (2017).
pubmed: 27913424
doi: 10.1152/ajplung.00326.2016
Schneider, J. P., Hegermann, J. & Wrede, C. Volume electron microscopy: analyzing the lung. Histochem. Cell Biol. 155, 241–260 (2021).
pubmed: 32944795
doi: 10.1007/s00418-020-01916-3
Willführ, A. et al. Estimation of the number of alveolar capillaries by the Euler number (Euler-Poincaré characteristic). Am. J. Physiol. Lung Cell Mol. Physiol. 309, L1286–L1293 (2015).
pubmed: 26432874
doi: 10.1152/ajplung.00410.2014
Buchacker, T. et al. Assessment of the alveolar capillary network in the postnatal mouse lung in 3D using serial block-face scanning electron microscopy. Front. Physiol. 10, 1357 (2019).
pubmed: 31824323
pmcid: 6881265
doi: 10.3389/fphys.2019.01357
Zeltner, T. B., Caduff, J. H., Gehr, P., Pfenninger, J. & Burri, P. H. The postnatal development and growth of the human lung. I. morphometry. Respir. Physiol. 67, 247–267 (1987).
pubmed: 3575905
doi: 10.1016/0034-5687(87)90057-0
Gehr, P., Bachofen, M. & Weibel, E. R. The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir. Physiol. 32, 121–140 (1978).
pubmed: 644146
doi: 10.1016/0034-5687(78)90104-4
Hsia, C. C., Hyde, D. M., Ochs, M., Weibel, E. R. & ATS/ERS Joint Task Force on Quantitative Assessment of Lung Structure. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am. J. Respir. Crit. Care Med. 181, 394–418 (2010).
pubmed: 20130146
pmcid: 5455840
doi: 10.1164/rccm.200809-1522ST
Ochs, M. & Mühlfeld, C. Quantitative microscopy of the lung: a problem-based approach. Part 1: basic principles of lung stereology. Am. J. Physiol. Lung Cell Mol. Physiol. 305, 15 (2013).
doi: 10.1152/ajplung.00429.2012
Mühlfeld, C. & Ochs, M. Quantitative microscopy of the lung: a problem-based approach. Part 2: stereological parameters and study designs in various diseases of the respiratory tract. Am. J. Physiol. Lung Cell Mol. Physiol. 305, 205 (2013).
doi: 10.1152/ajplung.00427.2012
Gundersen, H. J. & Jensen, E. B. The efficiency of systematic sampling in stereology and its prediction. J. Microsc. 147, 229–263 (1987).
pubmed: 3430576
doi: 10.1111/j.1365-2818.1987.tb02837.x
Rößler, G. et al. Prematurity and hyperoxia have different effects on alveolar and microvascular lung development in the rabbit. J. Histochem. Cytochem. 71, 259–271 (2023).
pubmed: 37199233
pmcid: 10227883
doi: 10.1369/00221554231177757
Nyengaard, J. R. Stereologic methods and their application in kidney research. J. Am. Soc. Nephrol. 10, 1100–1123 (1999).
pubmed: 10232698
doi: 10.1681/ASN.V1051100
Grothausmann, R., Zukić, D., McCormick, M., Mühlfeld, C. & Knudsen, L. Enabling Manual Intervention for Otherwise Automated Registration of Large Image Series. In Biomedical Image Registration. WBIR 2020. (Špiclin, Ž., McClelland, J., Kybic, J., Goksel, O., eds) 23–33 (Springer, Cham, 2020) https://doi.org/10.1007/978-3-030-50120-4_3 .
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
pubmed: 22743772
doi: 10.1038/nmeth.2019
Marstal, K., Berendsen, F., Staring, M., Klein, S. SimpleElastix: A User-Friendly, Multi-lingual Library for Medical Image Registration. Proc. IEEE Conf. Comput. Vision Pattern Recognit. 574–582 https://doi.org/10.1109/CVPRW.2016.78 (2016).
Yushkevich, P. A. et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. NeuroImage 31, 1116–1128 (2006).
pubmed: 16545965
doi: 10.1016/j.neuroimage.2006.01.015
Hernandez-Cerdan, P. SGEXT: Spatial Graph Extractor (0.9.15). (Zenodo 2021) https://doi.org/10.5281/zenodo.5040457 .
Ahrens, J., Geveci, B., Law, C. ParaView: An End-User Tool for Large Data Visualization. In Visualization Handbook (Hansen, C. D. & Johnson C. R., eds) 717–731 (Elsevier, 2005). https://doi.org/10.1016/B978-012387582-2/50038-1 .
Thurlbeck, W. M. Lung growth and alveolar multiplication. Pathobiol. Annu. 5, 1–34 (1975).
pubmed: 1105318
Thurlbeck, W. M. & Angus, G. E. Growth and aging of the normal human lung. Chest 67, 3S–6S (1975).
pubmed: 1112103
doi: 10.1378/chest.67.2_Supplement.3S
Burri, P. H. Structural aspects of postnatal lung development - alveolar formation and growth. Biol. Neonate 89, 313–322 (2006).
pubmed: 16770071
doi: 10.1159/000092868
Mund, S. I., Stampanoni, M. & Schittny, J. C. Developmental alveolarization of the mouse lung. Dev. Dyn. 237, 2108–2116 (2008).
pubmed: 18651668
doi: 10.1002/dvdy.21633
Branchfield, K. et al. A three-dimensional study of alveologenesis in mouse lung. Dev. Biol. 409, 429–441 (2016).
pubmed: 26632490
doi: 10.1016/j.ydbio.2015.11.017
Grothausmann, R. et al. Combination of µCT and light microscopy for generation-specific stereological analysis of pulmonary arterial branches: a proof-of-concept study. Histochem. Cell Biol. 155, 227–239 (2021).
pubmed: 33263790
doi: 10.1007/s00418-020-01946-x
Labode, J. et al. Evaluation of classifications of the monopodial bronchopulmonary vasculature using clustering methods. Histochem. Cell Biol. 158, 435–445 (2022).
pubmed: 35739424
pmcid: 9630218
doi: 10.1007/s00418-022-02116-x
Labode, J. et al. Location-specific pathology analysis of the monopodial pulmonary vasculature in a rabbit model of bronchopulmonary dysplasia-A pilot study. Physiol. Rep. 11, e15747 (2023).
pubmed: 37358021
pmcid: 10291732
doi: 10.14814/phy2.15747
Caduff, J. H., Fischer, L. C. & Burri, P. H. Scanning electron microscope study of the developing microvasculature in the postnatal rat lung. Anat. Rec. 216, 154–164 (1986).
pubmed: 3777448
doi: 10.1002/ar.1092160207
Roth-Kleiner, M., Berger, T. M., Tarek, M. R., Burri, P. H. & Schittny, J. C. Neonatal dexamethasone induces premature microvascular maturation of the alveolar capillary network. Dev. Dyn. 233, 1261–1271 (2005).
pubmed: 15937935
doi: 10.1002/dvdy.20447
Roth-Kleiner, M. & Post, M. Similarities and dissimilarities of branching and septation during lung development. Ped. Pulmonol. 40, 113–134 (2005).
doi: 10.1002/ppul.20252
Abman, S. H. Bronchopulmonary dysplasia: “a vascular hypothesis. Am. J. Respir. Crit. Care Med. 164, 1755–1756 (2001).
pubmed: 11734417
doi: 10.1164/ajrccm.164.10.2109111c
Bhatt, A. J. et al. Disrupted pulmonary vasculature and decreased vascular endothelial growth factor, Flt-1, and TIE-2 in human infants dying with bronchopulmonary dysplasia. Am. J. Respir. Crit. Care Med. 164, 1971–1980 (2001).
pubmed: 11734454
doi: 10.1164/ajrccm.164.10.2101140
McGrath-Morrow, S. A. et al. Vascular endothelial growth factor receptor 2 blockade disrupts postnatal lung development. Am. J. Respir. Cell Mol. Biol. 32, 420–427 (2005).
pubmed: 15722510
doi: 10.1165/rcmb.2004-0287OC
Tschanz, S. A., Damke, B. M. & Burri, P. H. Influence of postnatally administered glucocorticoids on rat lung growth. Biol. Neonat. 68, 229–245 (1995).
doi: 10.1159/000244241
Tschanz, S. A., Haenni, B. & Burri, P. H. Glucocorticoid induced impairment of lung structure assessed by digital image analysis. Eur. J. Pediatr. 161, 26–30 (2002).
pubmed: 11808877
doi: 10.1007/s00431-001-0852-1
Schittny, J. C., Djonov, V., Fine, A. & Burri, P. H. Programmed cell death contributes to postnatal lung development. Am. J. Respir. Cell Mol. Biol. 18, 786–793 (1998).
pubmed: 9618383
doi: 10.1165/ajrcmb.18.6.3031
Mokhtar, D. M., Hussein, M. T., Hussein, M. M., Abd-Elhafez, E. A. & Kamel, G. New insight into the development of the respiratory acini in rabbits: morphological, electron microscopic studies, and TUNEL assay. Microsc. Microanal. 25, 769–785 (2019).
pubmed: 30761973
doi: 10.1017/S1431927619000059