Research ArticleMyocardial Infarction

Donor Myocardial Infarction Impairs the Therapeutic Potential of Bone Marrow Cells by an Interleukin-1–Mediated Inflammatory Response

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Science Translational Medicine  14 Sep 2011:
Vol. 3, Issue 100, pp. 100ra90
DOI: 10.1126/scitranslmed.3002814

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Delivery of bone marrow cells (BMCs) to the heart has substantially improved cardiac function in most rodent models of myocardial infarction (MI), but clinical trials of BMC therapy have led to only modest improvements. Rodent models typically involve intramyocardial injection of BMCs from distinct donor individuals who are healthy. In contrast, autologous BMCs from individuals after MI are used for clinical trials. Using BMCs from donor mice after MI, we discovered that recent MI impaired BMC therapeutic efficacy. MI led to myocardial inflammation and an increased inflammatory state in the bone marrow, changing the BMC composition and reducing their efficacy. Injection of a general anti-inflammatory drug or a specific interleukin-1 inhibitor to donor mice after MI prevented this impairment. Our findings offer an explanation of why human trials have not matched the success of rodent experiments and suggest potential strategies to improve the success of clinical autologous BMC therapy.


  • * Present address: Department of Cardiology, Imizu City Hospital, Imizu City, Toyama 934-0053, Japan.

  • Present address: Silver Creek Pharmaceuticals, San Francisco, CA 94158, USA.

  • Present address: Boston University School of Medicine, Boston, MA 02118, USA.

  • § Present address: MacroGenics Inc., South San Francisco, CA 94080, USA.

  • || Present address: Department of Medicine, Stanford University, Stanford, CA 94305, USA.

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