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Respir Res. 2017 Jun 30;18(1):132. doi: 10.1186/s12931-017-0611-0.

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

Author information

1
Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, 1060 William Moore Drive, RB306, Raleigh, NC 27607, NC, USA.
2
Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh/Chapel Hill, NC, USA.
3
Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
4
Divisions of Cardiothoracic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
5
Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
6
Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, 1060 William Moore Drive, RB306, Raleigh, NC 27607, NC, USA. kcheng3@ncsu.edu.
7
Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh/Chapel Hill, NC, USA. kcheng3@ncsu.edu.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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).

KEYWORDS:

Lung spheroid; Pulmonary progenitor cells; Stem cell

PMID:
28666430
PMCID:
PMC5493087
DOI:
10.1186/s12931-017-0611-0
[Indexed for MEDLINE]
Free PMC Article

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