eCite Digital Repository

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

Citation

Zhang, Y and Sivakumaran, P and Newcomb, AE and Hernandez, D and Harris, N and Khanabdali, R and Liu, GS and Kelly, DJ and Pebay, A and Hewitt, AW and Boyle, A and Harvey, R and Morrison, WA and Elliott, DA and Dusting, GJ and Lim, SY, Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart, Stem Cell, 33, (10) pp. 3100-3113. ISSN 1945-4570 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 AlphaMed

DOI: doi:10.1002/stem.2101

Abstract

Cardiac resident stem cells (CRSCs) hold much promise to treat heart disease but this remains a controversial field. Here, we describe a novel population of CRSCs, which are positive for W8B2 antigen and were obtained from adult human atrial appendages. W8B2(+) CRSCs exhibit a spindle-shaped morphology, are clonogenic and capable of self-renewal. W8B2(+) CRSCs show high expression of mesenchymal but not hematopoietic nor endothelial markers. W8B2(+) CRSCs expressed GATA4, HAND2, and TBX5, but not C-KIT, SCA-1, NKX2.5, PDGFRα, ISL1, or WT1. W8B2(+) CRSCs can differentiate into cardiovascular lineages and secrete a range of cytokines implicated in angiogenesis, chemotaxis, inflammation, extracellular matrix remodeling, cell growth, and survival. In vitro, conditioned medium collected from W8B2(+) CRSCs displayed prosurvival, proangiogenic, and promigratory effects on endothelial cells, superior to that of other adult stem cells tested, and additionally promoted survival and proliferation of neonatal rat cardiomyocytes. Intramyocardial transplantation of human W8B2(+) CRSCs into immunocompromised rats 1 week after myocardial infarction markedly improved cardiac function (∼40% improvement in ejection fraction) and reduced fibrotic scar tissue 4 weeks after infarction. Hearts treated with W8B2(+) CRSCs showed less adverse remodeling of the left ventricle, a greater number of proliferating cardiomyocytes (Ki67(+) cTnT(+) cells) in the remote region, higher myocardial vascular density, and greater infiltration of CD163(+) cells (a marker for M2 macrophages) into the border zone and scar regions. In summary, W8B2(+) CRSCs are distinct from currently known CRSCs found in human hearts, and as such may be an ideal cell source to repair myocardial damage after infarction.

Item Details

Item Type:Refereed Article
Keywords:Adult stem cells, Heart, Mesenchymal stem cell, Myocardial infarction, W8B2
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
Author:Hewitt, AW (Dr Alex Hewitt)
ID Code:113168
Year Published:2015
Web of Science® Times Cited:12
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-12-14
Last Modified:2017-03-23
Downloads:0

Repository Staff Only: item control page