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Cathelicidin Related Antimicrobial Peptide (CRAMP) Enhances Bone Marrow Cell Retention and Attenuates Cardiac Dysfunction in a Mouse Model of Myocardial Infarction
Journal article   Open access   Peer reviewed

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, …
Stem cell reviews and reports, v 14(5), pp 702-714
Oct 2018
DOI: https://doi.org/10.1007/s12015-018-9833-x
PMID: 29948752
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc6119631View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Animals Antimicrobial Cationic Peptides - administration & dosage Antimicrobial Cationic Peptides - metabolism Bone Marrow Transplantation Disease Models, Animal Humans Leukocytes, Mononuclear - metabolism Leukocytes, Mononuclear - transplantation Male Mice Myocardial Infarction - physiopathology Myocardial Infarction - therapy Regenerative Medicine Retention, Psychology - drug effects
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. 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. 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. 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.

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15 citations in Web of Science
19 citations in Scopus

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell & Tissue Engineering
Cell Biology
Medicine, Research & Experimental
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