In Vitro Grown Micro-Tissues for Cardiac Cell Replacement Therapy in Vivo.
Animals
Bone Marrow Cells
/ cytology
Cell Line
Cell Tracking
Coculture Techniques
Immunity, Innate
Male
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells
/ cytology
Mice
Microscopy, Fluorescence
Myocardial Infarction
/ pathology
Myocardium
/ immunology
Myocytes, Cardiac
/ cytology
Neutrophil Infiltration
Optical Imaging
Pluripotent Stem Cells
/ cytology
Polymers
/ chemistry
Cardiac cell therapy
Cardiomyocytes
Embryonic stem cells
Induced pluripotent stem cells
Reconstructive medicine
Regenerative medicine
Thermo-responsive polymer
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221
Informations de publication
Date de publication:
2019
2019
Historique:
received:
14
09
2018
accepted:
29
04
2019
entrez:
4
5
2019
pubmed:
3
5
2019
medline:
15
5
2019
Statut:
ppublish
Résumé
Different approaches have been considered to improve heart reconstructive medicine and direct delivery of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) appears to be highly promising in this context. However, low cell persistence post-transplantation remains a bottleneck hindering the approach. Here, we present a novel strategy to overcome the low engraftment of PSC-CMs during the early post-transplantation phase into the myocardium of both healthy and cryoinjured syngeneic mice. Adult murine bone marrow mesenchymal stem cells (MSCs) and PSC-CMs were co-cultured on thermo-responsive polymers and later detached through temperature reduction, resulting in the protease-free generation of cell clusters (micro-tissues) composed of both cells types. Micro-tissues were transplanted into healthy and cryo-injured murine hearts. Short term cell retention was quantified by real-time-PCR. Longitudinal cell tracking was performed by bioluminescence imaging for four weeks. Transplanted cells were further detected by immunofluorescence staining of tissue sections. We demonstrated that in vitro grown micro-tissues consisting of PSC-CMs and MSCs can increase cardiomyocyte retention by >10fold one day post-transplantation, but could not fully rescue a further cell loss between day 1 and day 2. Neutrophil infiltration into the transplanted area was detected in healthy hearts and could be attributed to the cellular implantation rather than tissue damage exerted by the transplantation cannula. Injected PSC-CMs were tracked and successfully detected for up to four weeks by bioluminescence imaging. This approach demonstrated that in vitro grown micro-tissues might contribute to the development of cardiac cell replacement therapies.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
Different approaches have been considered to improve heart reconstructive medicine and direct delivery of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) appears to be highly promising in this context. However, low cell persistence post-transplantation remains a bottleneck hindering the approach. Here, we present a novel strategy to overcome the low engraftment of PSC-CMs during the early post-transplantation phase into the myocardium of both healthy and cryoinjured syngeneic mice.
METHODS
METHODS
Adult murine bone marrow mesenchymal stem cells (MSCs) and PSC-CMs were co-cultured on thermo-responsive polymers and later detached through temperature reduction, resulting in the protease-free generation of cell clusters (micro-tissues) composed of both cells types. Micro-tissues were transplanted into healthy and cryo-injured murine hearts. Short term cell retention was quantified by real-time-PCR. Longitudinal cell tracking was performed by bioluminescence imaging for four weeks. Transplanted cells were further detected by immunofluorescence staining of tissue sections.
RESULTS
RESULTS
We demonstrated that in vitro grown micro-tissues consisting of PSC-CMs and MSCs can increase cardiomyocyte retention by >10fold one day post-transplantation, but could not fully rescue a further cell loss between day 1 and day 2. Neutrophil infiltration into the transplanted area was detected in healthy hearts and could be attributed to the cellular implantation rather than tissue damage exerted by the transplantation cannula. Injected PSC-CMs were tracked and successfully detected for up to four weeks by bioluminescence imaging.
CONCLUSION
CONCLUSIONS
This approach demonstrated that in vitro grown micro-tissues might contribute to the development of cardiac cell replacement therapies.
Substances chimiques
Polymers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1309-1324Subventions
Organisme : Else Kröner-Fresenius-Stiftung
ID : 2012_A143
Pays : Germany
Informations de copyright
© Copyright by the Author(s). Published by Cell Physiol Biochem Press.
Déclaration de conflit d'intérêts
The authors declare to have no competing interests.