TY - JOUR
T1 - Retention and functional effect of adipose-derived stromal cells administered in alginate hydrogel in a rat model of acute myocardial infarction
AU - Follin, Bjarke
AU - Ghotbi, Adam Ali
AU - Clemmensen, Andreas Ettrup
AU - Bentsen, Simon
AU - Juhl, Morten
AU - Søndergaard, Rebekka Harary
AU - Lund, Lisbeth Drozd
AU - Haack-Sørensen, Mandana
AU - Hasbak, Philip
AU - Cohen, Smadar
AU - Ripa, Rasmus Sejersten
AU - Kastrup, Jens
AU - Ekblond, Annette
AU - Kjær, Andreas
N1 - Funding Information:
The authors thank Dr. Claus Andersen and Dr. Eric Santoni-Rugiu from the Department of Pathology, Rigshospitalet, Copenhagen, Denmark, for their support on histology and interpretation of results. The authors thank Assistant Professor Jiyang Kim from DanStem, University of Copenhagen, Denmark, and Professor Gambhir from Stanford University, USA, for kindly allowing us to use the luciferase2-TdTomato (L2T) plasmid. The authors thank Professor Søren Buus’ group at the Department of Immunology and Microbiology, University of Copenhagen, Denmark, for propagation of the plasmid and thank Associate Professor Frederik Vilhardt from the Vilhardt Group, at the University of Copenhagen for the transduction of the L2T plasmids into the human ASC lines. The authors thank Associate Professor Anders Elm Pedersen from the Department of Immunology and Microbiology, University of Copenhagen, Denmark, and Liselotte Rothmann Norup from the Flow Cytometry Core Facility at the University of Copenhagen, Denmark, for their help with the cell sorting of the L2T-positive hASCs. The authors thank Kasper With Nielsen for his help with the animals and Michelle Westergaard Kaijer and Lotte Kellemann Kristensen for their excellent assistance with histology, all from the Cluster for Molecular Imaging, University of Copenhagen, Denmark. The authors thank Kirstine Joo Andresen and Mojdeh Lotfi from the Cardiology Stem Cell Centre for lab assistance. This work was funded by the Innovation Fund Denmark as well as by Kirsten og Freddy Johansens Fond.
Publisher Copyright:
Copyright © 2018 Bjarke Follin et al.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background. Cell therapy for heart disease has been proven safe and efficacious, despite poor cell retention in the injected area. Improving cell retention is hypothesized to increase the treatment effect. In the present study, human adipose-derived stromal cells (ASCs) were delivered in an in situ forming alginate hydrogel following acute myocardial infarction (AMI) in rats. Methods. ASCs were transduced with luciferase and tested for ASC phenotype. AMI was inducted in nude rats, with subsequent injection of saline (controls), 1 × 106 ASCs in saline or 1 × 106 ASCs in 1% (w/v) alginate hydrogel. ASCs were tracked by bioluminescence and functional measurements were assessed by magnetic resonance imaging (MRI) and 82rubidium positron emission tomography (PET). Results. ASCs in both saline and alginate hydrogel significantly increased the ejection fraction (7.2% and 7.8% at 14 days and 7.2% and 8.0% at 28 days, resp.). After 28 days, there was a tendency for decreased infarct area and increased perfusion, compared to controls. No significant differences were observed between ASCs in saline or alginate hydrogel, in terms of retention and functional salvage. Conclusion. ASCs improved the myocardial function after AMI, but administration in the alginate hydrogel did not further improve retention of the cells or myocardial function.
AB - Background. Cell therapy for heart disease has been proven safe and efficacious, despite poor cell retention in the injected area. Improving cell retention is hypothesized to increase the treatment effect. In the present study, human adipose-derived stromal cells (ASCs) were delivered in an in situ forming alginate hydrogel following acute myocardial infarction (AMI) in rats. Methods. ASCs were transduced with luciferase and tested for ASC phenotype. AMI was inducted in nude rats, with subsequent injection of saline (controls), 1 × 106 ASCs in saline or 1 × 106 ASCs in 1% (w/v) alginate hydrogel. ASCs were tracked by bioluminescence and functional measurements were assessed by magnetic resonance imaging (MRI) and 82rubidium positron emission tomography (PET). Results. ASCs in both saline and alginate hydrogel significantly increased the ejection fraction (7.2% and 7.8% at 14 days and 7.2% and 8.0% at 28 days, resp.). After 28 days, there was a tendency for decreased infarct area and increased perfusion, compared to controls. No significant differences were observed between ASCs in saline or alginate hydrogel, in terms of retention and functional salvage. Conclusion. ASCs improved the myocardial function after AMI, but administration in the alginate hydrogel did not further improve retention of the cells or myocardial function.
UR - http://www.scopus.com/inward/record.url?scp=85056076223&partnerID=8YFLogxK
U2 - 10.1155/2018/7821461
DO - 10.1155/2018/7821461
M3 - Article
AN - SCOPUS:85056076223
SN - 1687-9678
VL - 2018
JO - Stem Cells International
JF - Stem Cells International
M1 - 7821461
ER -
