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Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.

Publication ,  Journal Article
Henry, E; Cores, J; Hensley, MT; Anthony, S; Vandergriff, A; de Andrade, JBM; Allen, T; Caranasos, TG; Lobo, LJ; Cheng, K
Published in: Stem Cells Transl Med
November 2015

UNLABELLED: Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture. Without antigenic sorting, the lung spheroids recapitulate the stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes. In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibited apoptosis, fibrosis, and infiltration but promoted angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperformed adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously, lung spheroid cells (the spheroid model) had only been used to study lung cancer cells. Our data suggest that lung spheroids and lung spheroid cells from healthy lung tissues are excellent sources of regenerative lung cells for therapeutic lung regeneration. SIGNIFICANCE: The results from the present study will lead to future human clinical trials using lung stem cell therapies to treat various incurable lung diseases, including pulmonary fibrosis. The data presented here also provide fundamental knowledge regarding how injected stem cells mediate lung repair in pulmonary fibrosis.

Duke Scholars

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Published In

Stem Cells Transl Med

DOI

ISSN

2157-6564

Publication Date

November 2015

Volume

4

Issue

11

Start / End Page

1265 / 1274

Location

England

Related Subject Headings

  • Spheroids, Cellular
  • Regeneration
  • Pulmonary Fibrosis
  • Mice, SCID
  • Mice
  • Mesenchymal Stem Cells
  • Mesenchymal Stem Cell Transplantation
  • Male
  • Humans
  • Heterografts
 

Citation

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Chicago
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Henry, E., Cores, J., Hensley, M. T., Anthony, S., Vandergriff, A., de Andrade, J. B. M., … Cheng, K. (2015). Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis. Stem Cells Transl Med, 4(11), 1265–1274. https://doi.org/10.5966/sctm.2015-0062
Henry, Eric, Jhon Cores, M Taylor Hensley, Shirena Anthony, Adam Vandergriff, James B. M. de Andrade, Tyler Allen, Thomas G. Caranasos, Leonard J. Lobo, and Ke Cheng. “Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.Stem Cells Transl Med 4, no. 11 (November 2015): 1265–74. https://doi.org/10.5966/sctm.2015-0062.
Henry E, Cores J, Hensley MT, Anthony S, Vandergriff A, de Andrade JBM, et al. Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis. Stem Cells Transl Med. 2015 Nov;4(11):1265–74.
Henry, Eric, et al. “Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.Stem Cells Transl Med, vol. 4, no. 11, Nov. 2015, pp. 1265–74. Pubmed, doi:10.5966/sctm.2015-0062.
Henry E, Cores J, Hensley MT, Anthony S, Vandergriff A, de Andrade JBM, Allen T, Caranasos TG, Lobo LJ, Cheng K. Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis. Stem Cells Transl Med. 2015 Nov;4(11):1265–1274.

Published In

Stem Cells Transl Med

DOI

ISSN

2157-6564

Publication Date

November 2015

Volume

4

Issue

11

Start / End Page

1265 / 1274

Location

England

Related Subject Headings

  • Spheroids, Cellular
  • Regeneration
  • Pulmonary Fibrosis
  • Mice, SCID
  • Mice
  • Mesenchymal Stem Cells
  • Mesenchymal Stem Cell Transplantation
  • Male
  • Humans
  • Heterografts