CCR2 macrophage response determines the functional outcome following cardiomyocyte transplantation

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Praveen Vasudevan - , Universitätsmedizin Rostock (Autor:in)
  • Markus Wolfien - , Institut für Medizinische Informatik und Biometrie, Center for Scalable Data Analytics and Artificial Intelligence (ScaDS.AI Dresden), Universität Rostock (Autor:in)
  • Heiko Lemcke - , Universitätsmedizin Rostock (Autor:in)
  • Cajetan Immanuel Lang - , Universitätsmedizin Rostock (Autor:in)
  • Anna Skorska - , Universitätsmedizin Rostock (Autor:in)
  • Ralf Gaebel - , Universitätsmedizin Rostock (Autor:in)
  • Anne-Marie Galow - , Institute of Genome Biology (Autor:in)
  • Dirk Koczan - , Universitätsmedizin Rostock (Autor:in)
  • Tobias Lindner - , Core Facility Multimodal Small Animal Imaging, Universitätsmedizin Rostock (Autor:in)
  • Wendy Bergmann - , Universitätsmedizin Rostock (Autor:in)
  • Brigitte Mueller-Hilke - , Universitätsmedizin Rostock (Autor:in)
  • Brigitte Vollmar - , Universitätsmedizin Rostock (Autor:in)
  • Bernd Joachim Krause - , Universitätsmedizin Rostock (Autor:in)
  • Olaf Wolkenhauer - , Universitätsmedizin Rostock (Autor:in)
  • Gustav Steinhoff - , Universitätsmedizin Rostock (Autor:in)
  • Robert David - , Universitätsmedizin Rostock (Autor:in)


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.


FachzeitschriftGenome medicine
PublikationsstatusVeröffentlicht - 10 Aug. 2023

Externe IDs

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


Fächergruppen, Lehr- und Forschungsbereiche, Fachgebiete nach Destatis


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