DOI: 10.1073/pnas.2132126100. Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction

Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction

10.1073/pnas.2132126100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Potential repair by cell grafting or mobilizing endogenous cells holds particular attraction in heart disease, where the meager capacity for cardiomyocyte proliferation likely contributes to the irreversibility of heart failure. Whether cardiac progenitors exist in adult myocardium itself is unanswered, as is the question whether undifferentiated cardiac precursor cells merely fuse with preexisting myocytes. Here we report the existence of adult heart-derived cardiac progenitor cells expressing stem cell antigen-1. Initially, the cells express neither cardiac structural genes nor Nkx2.5 but differentiate in vitro in response to 5′-azacytidine, in part depending on Bmpr1a , a receptor for bone morphogenetic proteins. Given intravenously after ischemia/reperfusion, cardiac stem cell antigen 1 cells home to injured myocardium. By using a Cre/Lox donor/recipient pair (α MHC-Cre / R26R ), differentiation was shown to occur roughly equally, with and without fusion to host cells.

Bibliography

Oh, H., Bradfute, S. B., Gallardo, T. D., Nakamura, T., Gaussin, V., Mishina, Y., Pocius, J., Michael, L. H., Behringer, R. R., Garry, D. J., Entman, M. L., & Schneider, M. D. (2003). Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction. Proceedings of the National Academy of Sciences, 100(21), 12313â12318.

Authors 12

Hidemasa Oh (first)
Steven B. Bradfute (additional)
Teresa D. Gallardo (additional)
Teruya Nakamura (additional)
Vinciane Gaussin (additional)
Yuji Mishina (additional)
Jennifer Pocius (additional)
Lloyd H. Michael (additional)
Richard R. Behringer (additional)
Daniel J. Garry (additional)
Mark L. Entman (additional)
Michael D. Schneider (additional)

References 37 Referenced 1,413

10.1172/JCI5298
10.1172/JCI12150
10.1038/35070587
10.1073/pnas.191217898
10.1161/01.CIR.0000051460.85800.BB
10.1056/NEJM200106073442303
10.1126/science.297.5585.1299
10.1126/science.1074807
10.1038/86439
10.1016/S0092-8674(01)00409-3
10.1016/S1534-5807(01)00049-1
10.1161/hc3501.093817
10.1073/pnas.181177898
10.1161/01.CIR.0000021923.58307.8F
10.1038/nature01539
10.1038/nature01531
10.1161/01.CIR.0000034046.87607.1C
10.1161/01.CIR.0000043246.74879.CD
10.1016/S0735-1097(03)00092-5
10.1152/ajpcell.2000.279.2.C429
10.1084/jem.183.4.1797
10.1073/pnas.032438799
10.1128/MCB.19.10.7096
10.1172/JCI8296
10.1073/pnas.042390499
10.1038/5007
Nossuli, T. O., Lakshminarayanan, V., Baumgarten, G., Taffet, G. E., Ballantyne, C. M., Michael, L. H. & Entman, M. L. (2000) Am. J. Physiol. 278, H1049–H1055. / Am. J. Physiol. (2000)
Soonpaa, M. H., Kim, K. K., Pajak, L., Franklin, M. & Field, L. J. (1996) Am. J. Physiol. 271, H2183–H2189.8945939 / Am. J. Physiol. (1996)
10.1083/jcb.200202092
10.1073/pnas.191169098
10.1126/science.1072530
10.1161/hc0102.101442
10.1038/nature00870
10.1172/JCI119509
10.1073/pnas.96.25.14482
10.1083/jcb.152.2.335
10.1016/S0301-472X(02)00954-2

Dates

Type	When
Created	21 years, 10 months ago (Oct. 14, 2003, 3:05 p.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 7:52 a.m.)
Indexed	1 day, 16 hours ago (Sept. 4, 2025, 10:28 a.m.)
Issued	21 years, 11 months ago (Oct. 6, 2003)
Published	21 years, 11 months ago (Oct. 6, 2003)
Published Online	21 years, 11 months ago (Oct. 6, 2003)
Published Print	21 years, 10 months ago (Oct. 14, 2003)

Funders 0

None

BibTeX

@article{Oh_2003, title={Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.2132126100}, DOI={10.1073/pnas.2132126100}, number={21}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Oh, Hidemasa and Bradfute, Steven B. and Gallardo, Teresa D. and Nakamura, Teruya and Gaussin, Vinciane and Mishina, Yuji and Pocius, Jennifer and Michael, Lloyd H. and Behringer, Richard R. and Garry, Daniel J. and Entman, Mark L. and Schneider, Michael D.}, year={2003}, month=oct, pages={12313–12318} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        9,
        4
      ]
    ],
    "date-time": "2025-09-04T14:28:09Z",
    "timestamp": 1756996089151
  },
  "reference-count": 37,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "21",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2003,
        10,
        14
      ]
    ]
  },
  "abstract": "<jats:p>\n            Potential repair by cell grafting or mobilizing endogenous cells holds particular attraction in heart disease, where the meager capacity for cardiomyocyte proliferation likely contributes to the irreversibility of heart failure. Whether cardiac progenitors exist in adult myocardium itself is unanswered, as is the question whether undifferentiated cardiac precursor cells merely fuse with preexisting myocytes. Here we report the existence of adult heart-derived cardiac progenitor cells expressing stem cell antigen-1. Initially, the cells express neither cardiac structural genes nor\n            <jats:italic>Nkx2.5</jats:italic>\n            but differentiate\n            <jats:italic>in vitro</jats:italic>\n            in response to 5\u2032-azacytidine, in part depending on\n            <jats:italic>Bmpr1a</jats:italic>\n            , a receptor for bone morphogenetic proteins. Given intravenously after ischemia/reperfusion, cardiac stem cell antigen 1 cells home to injured myocardium. By using a Cre/Lox donor/recipient pair (\u03b1\n            <jats:italic>MHC-Cre</jats:italic>\n            /\n            <jats:italic>R26R</jats:italic>\n            ), differentiation was shown to occur roughly equally, with and without fusion to host cells.\n          </jats:p>",
  "DOI": "10.1073/pnas.2132126100",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2003,
        10,
        14
      ]
    ],
    "date-time": "2003-10-14T19:05:46Z",
    "timestamp": 1066158346000
  },
  "page": "12313-12318",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 1413,
  "title": "Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction",
  "prefix": "10.1073",
  "volume": "100",
  "author": [
    {
      "given": "Hidemasa",
      "family": "Oh",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Steven B.",
      "family": "Bradfute",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Teresa D.",
      "family": "Gallardo",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Teruya",
      "family": "Nakamura",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Vinciane",
      "family": "Gaussin",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Yuji",
      "family": "Mishina",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Jennifer",
      "family": "Pocius",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Lloyd H.",
      "family": "Michael",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Richard R.",
      "family": "Behringer",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Daniel J.",
      "family": "Garry",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Mark L.",
      "family": "Entman",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    },
    {
      "given": "Michael D.",
      "family": "Schneider",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Cardiovascular Development, Center for Cell and Gene Therapy, DeBakey Heart Center, and Departments of Medicine, Immunology,Molecular and Cellular Biology, and Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030; Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103; National Institute of Environmental Health Sciences, Research..."
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2003,
        10,
        6
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI5298"
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI12150"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35070587"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.191217898"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1161/01.CIR.0000051460.85800.BB"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1056/NEJM200106073442303"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.297.5585.1299"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1074807"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/86439"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(01)00409-3"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1534-5807(01)00049-1"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1161/hc3501.093817"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.181177898"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1161/01.CIR.0000021923.58307.8F"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature01539"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature01531"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1161/01.CIR.0000034046.87607.1C"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1161/01.CIR.0000043246.74879.CD"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0735-1097(03)00092-5"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1152/ajpcell.2000.279.2.C429"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1084/jem.183.4.1797"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.032438799"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.19.10.7096"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI8296"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.042390499"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/5007"
    },
    {
      "key": "e_1_3_2_27_2",
      "first-page": "H1049",
      "volume": "278",
      "year": "2000",
      "unstructured": "Nossuli, T. O., Lakshminarayanan, V., Baumgarten, G., Taffet, G. E., Ballantyne, C. M., Michael, L. H. & Entman, M. L. (2000) Am. J. Physiol. 278, H1049\u2013H1055.",
      "journal-title": "Am. J. Physiol."
    },
    {
      "key": "e_1_3_2_28_2",
      "first-page": "H2183",
      "volume": "271",
      "year": "1996",
      "unstructured": "Soonpaa, M. H., Kim, K. K., Pajak, L., Franklin, M. & Field, L. J. (1996) Am. J. Physiol. 271, H2183\u2013H2189.8945939",
      "journal-title": "Am. J. Physiol."
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.200202092"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.191169098"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1072530"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1161/hc0102.101442"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature00870"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI119509"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.96.25.14482"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.152.2.335"
    },
    {
      "key": "e_1_3_2_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0301-472X(02)00954-2"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.2132126100",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        13
      ]
    ],
    "date-time": "2022-04-13T11:52:17Z",
    "timestamp": 1649850737000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.2132126100"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2003,
        10,
        6
      ]
    ]
  },
  "references-count": 37,
  "journal-issue": {
    "issue": "21",
    "published-print": {
      "date-parts": [
        [
          2003,
          10,
          14
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.2132126100"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.2132126100",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2003,
        10,
        6
      ]
    ]
  },
  "assertion": [
    {
      "value": "2003-04-11",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2003-10-06",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}