Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies.

Journal Article (Journal Article)


Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality.


In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery.


From one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days.


Here, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

Full Text

Duke Authors

Cited Authors

  • Dinh, P-UC; Cores, J; Hensley, MT; Vandergriff, AC; Tang, J; Allen, TA; Caranasos, TG; Adler, KB; Lobo, LJ; Cheng, K

Published Date

  • June 2017

Published In

Volume / Issue

  • 18 / 1

Start / End Page

  • 132 -

PubMed ID

  • 28666430

Pubmed Central ID

  • PMC5493087

Electronic International Standard Serial Number (EISSN)

  • 1465-993X

International Standard Serial Number (ISSN)

  • 1465-9921

Digital Object Identifier (DOI)

  • 10.1186/s12931-017-0611-0


  • eng