Cardiomyocyte transplantation after myocardial infarction alters the immune response in the heart

Praveen Vasudevan; Markus Wolfien; Heiko Lemcke; Cajetan Immanuel Lang; Anna Skorska; Ralf Gaebel; Dirk Koczan; Tobias Lindner; Robby Engelmann; Brigitte Vollmar; Bernd Joachim Krause; Olaf Wolkenhauer; Hermann Lang; Gustav Steinhoff; Robert David

doi:10.3390/cells9081825

Cardiomyocyte transplantation after myocardial infarction alters the immune response in the heart

Praveen Vasudevan, Markus Wolfien, Heiko Lemcke, Cajetan Immanuel Lang, Anna Skorska, Ralf Gaebel, Dirk Koczan, Tobias Lindner, Robby Engelmann, Brigitte Vollmar, Bernd Joachim Krause, Olaf Wolkenhauer, Hermann Lang, Gustav Steinhoff, Robert David^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as a result of syngeneic neonatal cardiomyocyte transplantation after MI leading to improved cardiac pump function as observed by magnetic resonance imaging in C57BL/6J mice. Interestingly, there was no improvement in the capillary density as well as infarct area as observed by CD31 and Sirius Red staining, respectively. Flow cytometric analysis revealed a significantly different response of monocyte-derived macrophages and regulatory T cells after cell transplantation. Interestingly, the inhibition of monocyte infiltration accompanied by cardiomyocyte transplantation diminished the positive effect of cell transplantation alone. The number of CD68+ macrophages in the remote area of the heart observed after four weeks was also different between the groups. Transcriptome analysis showed several changes in the gene expression involving circadian regulation, mitochondrial metabolism and immune responses after cardiomyocyte transplantation. Conclusion: Our work shows that cardiomyocyte transplantation alters the immune response after myocardial infarction with the recruited monocytes playing a role in the beneficial effect of cell transplantation. It also paves the way for further optimization of the efficacy of cardiomyocyte transplantation and their successful translation in the clinic.

Original language	English
Article number	1825
Pages (from-to)	1-18
Number of pages	18
Journal	Cells
Volume	9
Issue number	8
DOIs	https://doi.org/10.3390/cells9081825
State	Published - Aug 2020
Externally published	Yes

Keywords

Cardiomyocytes
Immune response
Infarction
Translation
Transplantation

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Vasudevan, P., Wolfien, M., Lemcke, H., Lang, C. I., Skorska, A., Gaebel, R., Koczan, D., Lindner, T., Engelmann, R., Vollmar, B., Krause, B. J., Wolkenhauer, O., Lang, H., Steinhoff, G., & David, R. (2020). Cardiomyocyte transplantation after myocardial infarction alters the immune response in the heart. Cells, 9(8), 1-18. Article 1825. https://doi.org/10.3390/cells9081825

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title = "Cardiomyocyte transplantation after myocardial infarction alters the immune response in the heart",

abstract = "We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as a result of syngeneic neonatal cardiomyocyte transplantation after MI leading to improved cardiac pump function as observed by magnetic resonance imaging in C57BL/6J mice. Interestingly, there was no improvement in the capillary density as well as infarct area as observed by CD31 and Sirius Red staining, respectively. Flow cytometric analysis revealed a significantly different response of monocyte-derived macrophages and regulatory T cells after cell transplantation. Interestingly, the inhibition of monocyte infiltration accompanied by cardiomyocyte transplantation diminished the positive effect of cell transplantation alone. The number of CD68+ macrophages in the remote area of the heart observed after four weeks was also different between the groups. Transcriptome analysis showed several changes in the gene expression involving circadian regulation, mitochondrial metabolism and immune responses after cardiomyocyte transplantation. Conclusion: Our work shows that cardiomyocyte transplantation alters the immune response after myocardial infarction with the recruited monocytes playing a role in the beneficial effect of cell transplantation. It also paves the way for further optimization of the efficacy of cardiomyocyte transplantation and their successful translation in the clinic.",

keywords = "Cardiomyocytes, Immune response, Infarction, Translation, Transplantation",

author = "Praveen Vasudevan and Markus Wolfien and Heiko Lemcke and Lang, \{Cajetan Immanuel\} and Anna Skorska and Ralf Gaebel and Dirk Koczan and Tobias Lindner and Robby Engelmann and Brigitte Vollmar and Krause, \{Bernd Joachim\} and Olaf Wolkenhauer and Hermann Lang and Gustav Steinhoff and Robert David",

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year = "2020",

month = aug,

doi = "10.3390/cells9081825",

language = "English",

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journal = "Cells",

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T1 - Cardiomyocyte transplantation after myocardial infarction alters the immune response in the heart

AU - Vasudevan, Praveen

AU - Wolfien, Markus

AU - Lemcke, Heiko

AU - Lang, Cajetan Immanuel

AU - Skorska, Anna

AU - Gaebel, Ralf

AU - Koczan, Dirk

AU - Lindner, Tobias

AU - Engelmann, Robby

AU - Vollmar, Brigitte

AU - Krause, Bernd Joachim

AU - Wolkenhauer, Olaf

AU - Lang, Hermann

AU - Steinhoff, Gustav

AU - David, Robert

PY - 2020/8

Y1 - 2020/8

N2 - We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as a result of syngeneic neonatal cardiomyocyte transplantation after MI leading to improved cardiac pump function as observed by magnetic resonance imaging in C57BL/6J mice. Interestingly, there was no improvement in the capillary density as well as infarct area as observed by CD31 and Sirius Red staining, respectively. Flow cytometric analysis revealed a significantly different response of monocyte-derived macrophages and regulatory T cells after cell transplantation. Interestingly, the inhibition of monocyte infiltration accompanied by cardiomyocyte transplantation diminished the positive effect of cell transplantation alone. The number of CD68+ macrophages in the remote area of the heart observed after four weeks was also different between the groups. Transcriptome analysis showed several changes in the gene expression involving circadian regulation, mitochondrial metabolism and immune responses after cardiomyocyte transplantation. Conclusion: Our work shows that cardiomyocyte transplantation alters the immune response after myocardial infarction with the recruited monocytes playing a role in the beneficial effect of cell transplantation. It also paves the way for further optimization of the efficacy of cardiomyocyte transplantation and their successful translation in the clinic.

AB - We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as a result of syngeneic neonatal cardiomyocyte transplantation after MI leading to improved cardiac pump function as observed by magnetic resonance imaging in C57BL/6J mice. Interestingly, there was no improvement in the capillary density as well as infarct area as observed by CD31 and Sirius Red staining, respectively. Flow cytometric analysis revealed a significantly different response of monocyte-derived macrophages and regulatory T cells after cell transplantation. Interestingly, the inhibition of monocyte infiltration accompanied by cardiomyocyte transplantation diminished the positive effect of cell transplantation alone. The number of CD68+ macrophages in the remote area of the heart observed after four weeks was also different between the groups. Transcriptome analysis showed several changes in the gene expression involving circadian regulation, mitochondrial metabolism and immune responses after cardiomyocyte transplantation. Conclusion: Our work shows that cardiomyocyte transplantation alters the immune response after myocardial infarction with the recruited monocytes playing a role in the beneficial effect of cell transplantation. It also paves the way for further optimization of the efficacy of cardiomyocyte transplantation and their successful translation in the clinic.

KW - Cardiomyocytes

KW - Immune response

KW - Infarction

KW - Translation

KW - Transplantation

UR - https://www.scopus.com/pages/publications/85089170371

U2 - 10.3390/cells9081825

DO - 10.3390/cells9081825

M3 - Article

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AN - SCOPUS:85089170371

SN - 2073-4409

VL - 9

SP - 1

EP - 18

JO - Cells

JF - Cells

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M1 - 1825

ER -

Cardiomyocyte transplantation after myocardial infarction alters the immune response in the heart

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