Cathelicidin Related Antimicrobial Peptide (CRAMP) Enhances Bone Marrow Cell Retention and Attenuates Cardiac Dysfunction in a Mouse Model of Myocardial Infarction

Yuri M. Klyachkin, Amr Idris, Christopher B. Rodell, Himi Tripathi, Shaojing Ye, Prabha Nagareddy, Ahmed Asfour, Erhe Gao, Rahul Annabathula, Mariusz Ratajczak, Jason A. Burdick, Ahmed Abdel-Latif

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Background: Acute myocardial infarction (MI) and the ensuing ischemic heart disease are approaching epidemic state. Unfortunately, no definitive therapies are available and human regenerative therapies have conflicting results. Limited stem cell retention following intracoronary administration has reduced the clinical efficacy of this novel therapy. Cathelicidin related antimicrobial peptides (CRAMPs) enhance chemotactic responsiveness of BMSPCs to low SDF-1 gradients, suggesting a potential role in BMSPCs engraftment. Here, we assessed the therapeutic efficacy of CRAMPs in the context of BMSPCs recruitment and retention via intracardiac delivery of CRAMP-treated BMSPCs or CRAMP-releasing hydrogels (HG) post-AMI. Methods: For cell transplantation experiments, mice were randomized into 3 groups: MI followed by injection of PBS, BMMNCs alone, and BMMNCs pre-incubated with CRAMP. During the in vivo HG studies, BM GFP chimera mice were randomized into 4 groups: MI followed by injection of HG alone, HG + SDF-1, HG + CRAMP, HG + SDF-1 + CRAMP. Changes in cardiac function at 5 weeks after MI were assessed using echocardiography. Angiogenesis was assessed using isolectin staining for capillary density. Results: Mice treated with BMMNCs pre-incubated with CRAMP had smaller scars, enhanced cardiac recovery and less adverse remodeling. Histologically, this group had higher capillary density. Similarly, sustained CRAMP release from hydrogels enhanced the therapeutic effect of SDF-1, leading to enhanced functional recovery, smaller scar size and higher capillary density. Conclusion: Cathelicidins enhance BMMNC retention and recruitment after intramyocardial administration post-AMI resulting in improvements in heart physiology and recovery. Therapies employing these strategies may represent an attractive method for improving outcomes of regenerative therapies in human studies.

Original languageEnglish
Pages (from-to)702-714
Number of pages13
JournalStem Cell Reviews and Reports
Issue number5
StatePublished - Oct 1 2018

Bibliographical note

Funding Information:
Acknowledgments Dr. Abdel-Latif is supported by the University of Kentucky Clinical and Translational Science Pilot Award (UL1TR000117), the UK COBRE Early Career Program (P20 GM103527) and the NIH Grant R56 HL124266. Dr. Nagareddy is supported by the NIH Pathway to Independence Award (1K99HL122505-01). Dr. Ye is supported by the T32 grant (HL091812). Dr. Ratajczak is supported by NIH grants 2R01 DK074720 and R01HL112788. Christopher B. Rodell is supported by an American Heart Association Predoctoral Fellowship. Jason A. Burdick is supported by an American Heart Association Established Investigator Award.

Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.


  • Bone marrow derived mononuclear cells (BMMNCs)
  • Cathelicidin related antimicrobial peptide (CRAMP)
  • LL-37
  • Myocardial infarction
  • Regeneration
  • Stem cells homing

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research


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