Enhancing myocardial repair with CardioClusters

Nat Commun. 2020 Aug 7;11(1):3955. doi: 10.1038/s41467-020-17742-z.


Cellular therapy to treat heart failure is an ongoing focus of intense research, but progress toward structural and functional recovery remains modest. Engineered augmentation of established cellular effectors overcomes impediments to enhance reparative activity. Such 'next generation' implementation includes delivery of combinatorial cell populations exerting synergistic effects. Concurrent isolation and expansion of three distinct cardiac-derived interstitial cell types from human heart tissue, previously reported by our group, prompted design of a 3D structure that maximizes cellular interaction, allows for defined cell ratios, controls size, enables injectability, and minimizes cell loss. Herein, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and c-Kit+ cardiac interstitial cells (cCICs) when cultured together spontaneously form scaffold-free 3D microenvironments termed CardioClusters. scRNA-Seq profiling reveals CardioCluster expression of stem cell-relevant factors, adhesion/extracellular-matrix molecules, and cytokines, while maintaining a more native transcriptome similar to endogenous cardiac cells. CardioCluster intramyocardial delivery improves cell retention and capillary density with preservation of cardiomyocyte size and long-term cardiac function in a murine infarction model followed 20 weeks. CardioCluster utilization in this preclinical setting establish fundamental insights, laying the framework for optimization in cell-based therapeutics intended to mitigate cardiomyopathic damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Capillaries / pathology
  • Cell Aggregation
  • Cell Death
  • Cell Lineage
  • Cell Size
  • Cellular Microenvironment*
  • Cytoprotection
  • Endothelial Progenitor Cells / cytology
  • Female
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Humans
  • Image Processing, Computer-Assisted
  • Infant, Newborn
  • Mesenchymal Stem Cells / cytology
  • Mice, Inbred NOD
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardium / pathology*
  • Myocytes, Cardiac / cytology
  • Oxidative Stress
  • Paracrine Communication
  • Rats, Sprague-Dawley
  • Transcription, Genetic
  • Wound Healing*