2004 Fiscal Year Final Research Report Summary
Regeneration of myocardium using bone marrow cells for the treatment of severe heart failure
| Project/Area Number |
14370423
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
SUGA Michiharu National Cardiovascular Center Research Institute, Regenerative Medicine and Tissue Engineering, 再生医療部, 室長 (80265397)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATANI Takeshi Organ Transplantation, 臓器移植部, 部長 (60155752)
HIDAKA Kyoko Bioscience, バイオサイエンス部, 室長 (00216681)
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| Project Period (FY) |
2002 – 2004
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| Keywords | cell transplantation therapy / bone marrow cell / paracrine mechanism / granulocyte-colony stimulating factor / arrhythmia / end-stage heart failure / contrast echocardiography |
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| Research Abstract |
In this project, we tried to elucidate the feasibility of cell-based therapy for severe heart failure, such as cardiac infarction and dilated cardiomyopathy (DCM) using autologous/syngeneic bone marrow cells (BMCs), which are not only technically established to collect cells but also immunologically and ethically thought to be acceptable.
i)Cell-based therapy for cardiac infarction : We clearly identified that transplanted BMCs into the infarct region differentiate to cardiomyocytes or coronary endothelial cells and induce the migration, differentiation and proliferation of endogenous stem cells by paracrine mechanisms, and thereby improve the function of recipient hearts. Furthermore, administration of granulocyte-colony stimulating factor (G-CSF) significantly promoted endogenous bone marrow stem cells to accumulate into the heart and differentiate to cardiomyocytes.
ii)Cell-based therapy for DCM : We revealed that BMC transplantation improved cardiac functions of doxorubicin-induced DCM rats. G-CSF injection at the early phase after doxorubicin treatment was also effective to enhance the migration of endogenous BMCs to the heart and raise the survival rate.
iii)Novel evaluation method and safety of the treatment : We reported the usefulness of myocardial contrast echocardiography to evaluate regional perfusion after BCM transplantation using a pig model. As for the safety of cell transplant therapy, we showed that porcine hearts are able to receive the injection of at least 10 ml of cell suspension without any adverse effects and cell therapy does not increase the susceptibility to arrhythmia in a rat DCM model.
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