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

13 Scopus citations

Abstract

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
Volume14
Issue number5
DOIs
StatePublished - Oct 1 2018

Bibliographical note

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

Keywords

  • 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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