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

Author information

Affiliations

  • 1. Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.
      Authors
    • Zhang Y 1
    • Hernandez D 1, 2
    • Kelly DJ 1
    (3 authors)
  • 2. O'Brien Institute Department, St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
      Authors
    • Sivakumaran P 2
    • Hernandez D 1, 2
    • Harris N 2
    • Khanabdali R 2, 3
    • Morrison WA 2, 3
    • Dusting GJ 2, 3, 4
    • Lim SY 2, 3
    (7 authors)
  • 3. Department of Surgery, St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.
      Authors
    • Newcomb AE 3
    • Khanabdali R 2, 3
    • Morrison WA 2, 3
    • Dusting GJ 2, 3, 4
    • Lim SY 2, 3
    (5 authors)
  • 4. Department of Ophthalmology, University of Melbourne, Melbourne, Victoria, Australia.
      Authors
    • Liu GS 4
    • Pébay A 4
    • Hewitt AW 4
    • Dusting GJ 2, 3, 4
    (4 authors)
  • 5. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
      Authors
    • Boyle A 5
    (1 author)
    • Show all (7)

ORCIDs linked to this article

Show all (9)

Stem Cells (Dayton, Ohio), 29 Jul 2015, 33(10):3100-3113
https://doi.org/10.1002/stem.2101 PMID: 26184084 

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.

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Read article at publisher's site: https://doi.org/10.1002/stem.2101

Read article for free, from open access legal sources, via Unpaywall: https://academic.oup.com/stmcls/article-pdf/33/10/3100/42016702/stmcls_33_10_3100.pdfUnpaywall

References 

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Funding 

Funders who supported this work.

ARC Special Initiative in Stem Cell Science (1)

National Health and Medical Research Council of Australia (3)