CCR2 macrophage response determines the functional outcome following cardiomyocyte transplantation

Research output: Contribution to journalResearch articleContributedpeer-review


  • Praveen Vasudevan - , University Medical Center Rostock (Author)
  • Markus Wolfien - , Institute for Medical Informatics and Biometry, Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI Dresden), University of Rostock (Author)
  • Heiko Lemcke - , University Medical Center Rostock (Author)
  • Cajetan Immanuel Lang - , University Medical Center Rostock (Author)
  • Anna Skorska - , University Medical Center Rostock (Author)
  • Ralf Gaebel - , University Medical Center Rostock (Author)
  • Anne-Marie Galow - , Institute of Genome Biology (Author)
  • Dirk Koczan - , University Medical Center Rostock (Author)
  • Tobias Lindner - , Core Facility Multimodal Small Animal Imaging, University Medical Center Rostock (Author)
  • Wendy Bergmann - , University Medical Center Rostock (Author)
  • Brigitte Mueller-Hilke - , University Medical Center Rostock (Author)
  • Brigitte Vollmar - , University Medical Center Rostock (Author)
  • Bernd Joachim Krause - , University Medical Center Rostock (Author)
  • Olaf Wolkenhauer - , University Medical Center Rostock (Author)
  • Gustav Steinhoff - , University Medical Center Rostock (Author)
  • Robert David - , University Medical Center Rostock (Author)


BACKGROUND: The immune response is a crucial factor for mediating the benefit of cardiac cell therapies. Our previous research showed that cardiomyocyte transplantation alters the cardiac immune response and, when combined with short-term pharmacological CCR2 inhibition, resulted in diminished functional benefit. However, the specific role of innate immune cells, especially CCR2 macrophages on the outcome of cardiomyocyte transplantation, is unclear.

METHODS: We compared the cellular, molecular, and functional outcome following cardiomyocyte transplantation in wildtype and T cell- and B cell-deficient Rag2del mice. The cardiac inflammatory response was assessed using flow cytometry. Gene expression profile was assessed using single-cell and bulk RNA sequencing. Cardiac function and morphology were determined using magnetic resonance tomography and immunohistochemistry respectively.

RESULTS: Compared to wildtype mice, Rag2del mice show an increased innate immune response at steady state and disparate macrophage response after MI. Subsequent single-cell analyses after MI showed differences in macrophage development and a lower prevalence of CCR2 expressing macrophages. Cardiomyocyte transplantation increased NK cells and monocytes, while reducing CCR2-MHC-IIlo macrophages. Consequently, it led to increased mRNA levels of genes involved in extracellular remodelling, poor graft survival, and no functional improvement. Using machine learning-based feature selection, Mfge8 and Ccl7 were identified as the primary targets underlying these effects in the heart.

CONCLUSIONS: Our results demonstrate that the improved functional outcome following cardiomyocyte transplantation is dependent on a specific CCR2 macrophage response. This work highlights the need to study the role of the immune response for cardiomyocyte cell therapy for successful clinical translation.


Original languageEnglish
Article number61
Number of pages1
JournalGenome medicine
Issue number1
Publication statusPublished - 10 Aug 2023

External IDs

Scopus 85167651668
Mendeley 7438b2f7-d2dd-37fe-aeb5-d792b429e516
ORCID /0000-0002-1887-4772/work/143075281


Research priority areas of TU Dresden

Subject groups, research areas, subject areas according to Destatis


  • Cell therapy, Immunocompromised, Machine learning, Macrophages, Myocardial infarction, Single-cell

Library keywords