Cardiac repair with a novel population of mesenchymal stem cells resident in the human heart

Journal article

Zhang, Yuan, Sivakumaran, Priyadharshini, Newcomb, Andrew, Hernandez, Damian, Harris, Nicole, Khanabdali, Ramin, Liu, Guei-Sheung, Kelly, Darren, Pebay, Alice, Hewitt, Alex, Boyle, Andrew, Harvey, Richard, Morrison, Wayne, Elliot, David, Dusting, Gregory and Lim, Shiang. (2015). Cardiac repair with a novel population of mesenchymal stem cells resident in the human heart. Stem Cells. 33(10), pp. 3100 - 3113. https://doi.org/10.1002/stem.2101
AuthorsZhang, Yuan, Sivakumaran, Priyadharshini, Newcomb, Andrew, Hernandez, Damian, Harris, Nicole, Khanabdali, Ramin, Liu, Guei-Sheung, Kelly, Darren, Pebay, Alice, Hewitt, Alex, Boyle, Andrew, Harvey, Richard, Morrison, Wayne, Elliot, David, Dusting, Gregory and Lim, Shiang
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. Stem Cells 2015;33:3100–3113

Year2015
JournalStem Cells
Journal citation33 (10), pp. 3100 - 3113
ISSN1066-5099
Digital Object Identifier (DOI)https://doi.org/10.1002/stem.2101
Page range3100 - 3113
Research GroupSports Performance, Recovery, Injury and New Technologies (SPRINT) Research Centre
Publisher's version
File Access Level
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Modulation of nicotinamide adenine dinucleotide phosphate oxidase expression and function by 3',4'-dihydroxyflavonol in phagocytic and vascular cells
Jiang, Fan, Guo, Nancy and Dusting, Gregory. (2008). Modulation of nicotinamide adenine dinucleotide phosphate oxidase expression and function by 3',4'-dihydroxyflavonol in phagocytic and vascular cells. Journal of Pharmacology and Experimental Therapeutics. 324(1), pp. 261 - 269. https://doi.org/10.1124/jpet.107.131433
Role of NADPH oxidase in tissue growth in a tissue engineering chamber in rats
Hachisuka, Hiroki, Dusting, Gregory J., Abberton, Keren M., Morrison, Wayne A. and Jiang, Fan. (2008). Role of NADPH oxidase in tissue growth in a tissue engineering chamber in rats. Journal of Tissue Engineering and Regenerative Medicine. 2(7), pp. 430 - 435. https://doi.org/10.1002/term.115
Myogel, a novel, basement membrane-rich, extracellular matrix derived from skeletal muscle, is highly adipogenic in vivo and in vitro
Abberton, Keren, Bortolotto, Susan K., Woods, Alan A., Findlay, Michael W., Morrison, Wayne, Thompson, Erik and Messina, Aurora. (2008). Myogel, a novel, basement membrane-rich, extracellular matrix derived from skeletal muscle, is highly adipogenic in vivo and in vitro. Cells, Tissues, Organs: in vivo, in vitro. 188(4), pp. 347 - 358. https://doi.org/10.1159/000121575
Low dose apolipoprotein A-I rescues carotid arteries from inflammation in vivo
Puranik, Rajesh, Bao, Shisan, Nobecourt, Estelle, Nicholls, Stephen J., Dusting, Gregory, Barter, Philip J., Celermajer, David Stephen and Rye, Kerry Anne. (2008). Low dose apolipoprotein A-I rescues carotid arteries from inflammation in vivo. Atherosclerosis. 196(1), pp. 240 - 247. https://doi.org/10.1016/j.atherosclerosis.2007.05.008
Early increase of Nox4 NADPH oxidase and superoxide generation following endothelin-1-induced stroke in conscious rats
McCann, Sarah K., Dusting, Gregory and Roulston, Carli L.. (2008). Early increase of Nox4 NADPH oxidase and superoxide generation following endothelin-1-induced stroke in conscious rats. Journal of Neuroscience Research. 86(11), pp. 2524 - 2534. https://doi.org/10.1002/jnr.21700
Reconstruction after external hemipelvectomy using tibia-hindfoot rotationplasty with calcaneo-sacral fixation
Kong, George Y. X., Rudiger, Hannes A., Ek, Eugene T. H., Morrison, Wayne and Choong, Peter F. M.. (2008). Reconstruction after external hemipelvectomy using tibia-hindfoot rotationplasty with calcaneo-sacral fixation. International Seminars in Surgical Oncology. 5(Article 1), pp. 1 - 4. https://doi.org/10.1186/1477-7800-5-1
Adipose differentiation of bone marrow-derived mesenchymal stem cells using Pluronic F-127 hydrogel in vitro
Vashi, Aditya V., Keramidaris, Efthimia, Abberton, Keren, Morrison, Wayne, Wilson, Jeremy L., O'Connor, Andrea J., Cooper-White, Justin J. and Thompson, Erik. (2008). Adipose differentiation of bone marrow-derived mesenchymal stem cells using Pluronic F-127 hydrogel in vitro. Biomaterials. 29(5), pp. 573 - 579. https://doi.org/10.1016/j.biomaterials.2007.10.017