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Endoscopic atomization of mesenchymal stromal cells : in vitro study for local cell therapy of the lungs

Thiebes, Anja Lena ; Uhl, Franziska E. LU ; Hauser, Marie ; Cornelissen, Christian G. ; Jockenhoevel, Stefan and Weiss, Daniel J. (2021) In Cytotherapy 23(4). p.293-300
Abstract

Background aims: Cell-based therapies of pulmonary diseases with mesenchymal stromal cells (MSCs) are increasingly under experimental investigation. In most of these, MSCs are administered intravenously or by direct intratracheal instillation. A parallel approach is to administer the cells into the lung by endoscopic atomization (spraying). In a previous study, the authors developed a flexible endoscopic atomization device that allows administration of respiratory epithelial cells in the lungs with high survival. Methods: In this study, the authors evaluated the feasibility of spraying MSCs with two different endoscopic atomization devices (air and pressure atomization). Following atomization, cell viability was evaluated with live/dead... (More)

Background aims: Cell-based therapies of pulmonary diseases with mesenchymal stromal cells (MSCs) are increasingly under experimental investigation. In most of these, MSCs are administered intravenously or by direct intratracheal instillation. A parallel approach is to administer the cells into the lung by endoscopic atomization (spraying). In a previous study, the authors developed a flexible endoscopic atomization device that allows administration of respiratory epithelial cells in the lungs with high survival. Methods: In this study, the authors evaluated the feasibility of spraying MSCs with two different endoscopic atomization devices (air and pressure atomization). Following atomization, cell viability was evaluated with live/dead staining. Subsequent effects on cytotoxicity, trilineage differentiation and expression of MSC-specific markers as well as on MSC metabolic activity and morphology were analyzed for up to 7 days. Results: MSC viability immediately after spraying and subsequent metabolic activity for 7 days was not influenced by either of the devices. Slightly higher cytotoxicity rates could be observed for pressure-atomized compared with control and air-atomized MSCs over 7 days. Flow cytometry revealed no changes in characteristic MSC cell surface marker expression, and morphology remained unchanged. Standard differentiation into osteocytes, chondrocytes and adipocytes was inducible after atomization. Conclusions: In the literature, a minimal survival of 50% was previously defined as the cutoff value for successful cell atomization. This is easily met with both of the authors’ devices, with more than 90% survival. Thus, there is a potential role for atomization in intrapulmonary MSC-based cell therapies, as it is a feasible and easily utilizable approach based on clinically available equipment.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
flow cytometry, lung, mesenchymal stem cells (MSCs), respiratory tract, stem cell transplantation
in
Cytotherapy
volume
23
issue
4
pages
293 - 300
publisher
Taylor & Francis
external identifiers
  • scopus:85100087681
  • pmid:33526382
ISSN
1465-3249
DOI
10.1016/j.jcyt.2020.12.010
language
English
LU publication?
yes
additional info
Funding Information: This study was funded by the i³tm Rotational Position Program of the Excellence Initiative of the German federal and state governments (ALT) and the German Research Foundation (DFG) (ALT and CGC; 394605884, CO1774/5-1). The study was also supported by the National Institutes of Health (DJW; ARRA RC4HL106625) and the National Heart, Lung, and Blood Institute (DJW; RO1 HL127144-01). The funding sources were not involved in study design, data collection, analysis and interpretation of data, writing of the article or decision to submit the article for publication. Funding Information: The authors thank D. Sumstad and Professor D. McKenna, University of Minnesota Medical Center, Minneapolis, MN, USA, and Professor W. Wagner, RWTH Aachen University, Aachen, Germany, for providing mesenchymal stromal cells and the Department of Orthopedic Surgery, University Hospital Aachen, Aachen, Germany, headed by Professor M. Tingart, for providing femoral heads for cell isolation. This study was supported by the Flow Cytometry Facility, a core facility of the Aachen Interdisciplinary Center for Clinical Research within the Faculty of Medicine at RWTH Aachen University. The authors thank Nathalie Steinke for setup of our flow cytometry protocols and her excellent technical assistance in performing the experiments. The authors also acknowledge the great technical assistance of Dr Michaela Bienert and Jake Dearborn. Publisher Copyright: © 2021 International Society for Cell & Gene Therapy Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
id
e9817266-6922-4f95-ac3d-df899b233df7
date added to LUP
2021-02-18 12:28:01
date last changed
2024-06-13 07:11:10
@article{e9817266-6922-4f95-ac3d-df899b233df7,
  abstract     = {{<p>Background aims: Cell-based therapies of pulmonary diseases with mesenchymal stromal cells (MSCs) are increasingly under experimental investigation. In most of these, MSCs are administered intravenously or by direct intratracheal instillation. A parallel approach is to administer the cells into the lung by endoscopic atomization (spraying). In a previous study, the authors developed a flexible endoscopic atomization device that allows administration of respiratory epithelial cells in the lungs with high survival. Methods: In this study, the authors evaluated the feasibility of spraying MSCs with two different endoscopic atomization devices (air and pressure atomization). Following atomization, cell viability was evaluated with live/dead staining. Subsequent effects on cytotoxicity, trilineage differentiation and expression of MSC-specific markers as well as on MSC metabolic activity and morphology were analyzed for up to 7 days. Results: MSC viability immediately after spraying and subsequent metabolic activity for 7 days was not influenced by either of the devices. Slightly higher cytotoxicity rates could be observed for pressure-atomized compared with control and air-atomized MSCs over 7 days. Flow cytometry revealed no changes in characteristic MSC cell surface marker expression, and morphology remained unchanged. Standard differentiation into osteocytes, chondrocytes and adipocytes was inducible after atomization. Conclusions: In the literature, a minimal survival of 50% was previously defined as the cutoff value for successful cell atomization. This is easily met with both of the authors’ devices, with more than 90% survival. Thus, there is a potential role for atomization in intrapulmonary MSC-based cell therapies, as it is a feasible and easily utilizable approach based on clinically available equipment.</p>}},
  author       = {{Thiebes, Anja Lena and Uhl, Franziska E. and Hauser, Marie and Cornelissen, Christian G. and Jockenhoevel, Stefan and Weiss, Daniel J.}},
  issn         = {{1465-3249}},
  keywords     = {{flow cytometry; lung; mesenchymal stem cells (MSCs); respiratory tract; stem cell transplantation}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{293--300}},
  publisher    = {{Taylor & Francis}},
  series       = {{Cytotherapy}},
  title        = {{Endoscopic atomization of mesenchymal stromal cells : in vitro study for local cell therapy of the lungs}},
  url          = {{http://dx.doi.org/10.1016/j.jcyt.2020.12.010}},
  doi          = {{10.1016/j.jcyt.2020.12.010}},
  volume       = {{23}},
  year         = {{2021}},
}