Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | 16281 |
| Fachzeitschrift | Scientific reports |
| Jahrgang | 8 |
| Publikationsstatus | Veröffentlicht - 2 Nov. 2018 |
Abstract
Macrophages are key cells of the innate immune system and act as tissue resident macrophages (TRMs) in the homeostasis of various tissues. Given their unique functions and therapeutic use as well as the feasibility to derive macrophages in vitro from hematopoietic stem cell (HSC) sources, we propose an “easy-to-use” immune cell spray (ICS) formulation to effectively deliver HSC-derived macrophages. To achieve this aim, we used classical pump spray devices to spray either the human myeloid cell line U937 or primary murine HSC-derived macrophages. For both cell types used, one puff could deliver cells with maintained morphology and functionality. Of note, cells tolerated the spraying process very well with a recovery of more than 90%. In addition, we used osmotic preconditioning to reduce the overall cell size of macrophages. While a 800 mosm hyperosmolar sucrose solution was able to reduce the cell size by 27%, we identified 600 mosm to be effective to reduce the cell size by 15% while maintaining macrophage morphology and functionality. Using an isolated perfused rat lung preparation, the combinatorial use of the ICS with preconditioned and genetically labeled U937 cells allowed the intra-pulmonary delivery of cells, thus paving the way for a new cell delivery platform.
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in: Scientific reports, Jahrgang 8, 16281, 02.11.2018.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - An immune cell spray (ICS) formulation allows for the delivery of functional monocyte/macrophages
AU - Beneke, Valerie
AU - Küster, Fennja
AU - Neehus, Anna Lena
AU - Hesse, Christina
AU - Lopez-Rodriguez, Elena
AU - Haake, Kathrin
AU - Rafiei Hashtchin, Anna
AU - Schott, Juliane Wilhelmine
AU - Walter, Dorothee
AU - Braun, Armin
AU - Wolkers, Willem F.
AU - Ackermann, Mania
AU - Lachmann, Nico
N1 - Funding Information: The authors thank Doreen Lüttge and Theresa Buchegger (Hannover Medical School) for excellent technical assistance. Moreover, we would like to thank Prof. Thomas Moritz for critical comments and his support. The authors also thank Daniela Paasch for providing genetically transduced human U937 cells. This work was financially supported by grants from the Deutsche Forschungsgemeinschaft: Cluster of Excellence REBIRTH (Exc 62/2) and the grant LA3680/2-1 (N.L.). The work was also funded by the Helmholtz excellence network REBIRTHt4s. Moreover, the work was supported by grants from the Federal Ministry of Education and Research (BMBF iMACnet 01EK1602A), the Else Kröner-Fresenius-Stiftung (EKFS): 2015_92 (N.L.) and 2016_A146 (M.A.). This work was also supported by a scholarship of the REBIRTH PhD program Regenerative Sciences (K.H.).
PY - 2018/11/2
Y1 - 2018/11/2
N2 - Macrophages are key cells of the innate immune system and act as tissue resident macrophages (TRMs) in the homeostasis of various tissues. Given their unique functions and therapeutic use as well as the feasibility to derive macrophages in vitro from hematopoietic stem cell (HSC) sources, we propose an “easy-to-use” immune cell spray (ICS) formulation to effectively deliver HSC-derived macrophages. To achieve this aim, we used classical pump spray devices to spray either the human myeloid cell line U937 or primary murine HSC-derived macrophages. For both cell types used, one puff could deliver cells with maintained morphology and functionality. Of note, cells tolerated the spraying process very well with a recovery of more than 90%. In addition, we used osmotic preconditioning to reduce the overall cell size of macrophages. While a 800 mosm hyperosmolar sucrose solution was able to reduce the cell size by 27%, we identified 600 mosm to be effective to reduce the cell size by 15% while maintaining macrophage morphology and functionality. Using an isolated perfused rat lung preparation, the combinatorial use of the ICS with preconditioned and genetically labeled U937 cells allowed the intra-pulmonary delivery of cells, thus paving the way for a new cell delivery platform.
AB - Macrophages are key cells of the innate immune system and act as tissue resident macrophages (TRMs) in the homeostasis of various tissues. Given their unique functions and therapeutic use as well as the feasibility to derive macrophages in vitro from hematopoietic stem cell (HSC) sources, we propose an “easy-to-use” immune cell spray (ICS) formulation to effectively deliver HSC-derived macrophages. To achieve this aim, we used classical pump spray devices to spray either the human myeloid cell line U937 or primary murine HSC-derived macrophages. For both cell types used, one puff could deliver cells with maintained morphology and functionality. Of note, cells tolerated the spraying process very well with a recovery of more than 90%. In addition, we used osmotic preconditioning to reduce the overall cell size of macrophages. While a 800 mosm hyperosmolar sucrose solution was able to reduce the cell size by 27%, we identified 600 mosm to be effective to reduce the cell size by 15% while maintaining macrophage morphology and functionality. Using an isolated perfused rat lung preparation, the combinatorial use of the ICS with preconditioned and genetically labeled U937 cells allowed the intra-pulmonary delivery of cells, thus paving the way for a new cell delivery platform.
UR - http://www.scopus.com/inward/record.url?scp=85056053059&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-34524-2
DO - 10.1038/s41598-018-34524-2
M3 - Article
C2 - 30389997
AN - SCOPUS:85056053059
VL - 8
JO - Scientific reports
JF - Scientific reports
SN - 2045-2322
M1 - 16281
ER -