Myocardial Repair Achieved by the Intramyocardial Implantation of Adult Cardiomyocytes in Combination with Bone Marrow Cells

Various cytokines produced by bone marrow cells can protect adult cardiomyocytes against apoptosis. Thus, we investigated the feasibility of implanting adult cardiomyocytes in combination with bone marrow cells for myocardial repair. Ventricular cardiomyocytes were isolated from adult rats and cocul...

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Main Authors: Tao-Sheng Li M.D., Ph.D., Masaya Takahashi, Mako Ohshima, Shu-Lan Qin, Masayuki Kubo, Keichi Muramatsu, Kimikazu Hamano
Format: Article
Language:English
Published: SAGE Publishing 2008-06-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368908786092702
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author Tao-Sheng Li M.D., Ph.D.
Masaya Takahashi
Mako Ohshima
Shu-Lan Qin
Masayuki Kubo
Keichi Muramatsu
Kimikazu Hamano
author_facet Tao-Sheng Li M.D., Ph.D.
Masaya Takahashi
Mako Ohshima
Shu-Lan Qin
Masayuki Kubo
Keichi Muramatsu
Kimikazu Hamano
author_sort Tao-Sheng Li M.D., Ph.D.
collection DOAJ
description Various cytokines produced by bone marrow cells can protect adult cardiomyocytes against apoptosis. Thus, we investigated the feasibility of implanting adult cardiomyocytes in combination with bone marrow cells for myocardial repair. Ventricular cardiomyocytes were isolated from adult rats and cocultured with bone marrow cells. Using a rat model of doxorubicin-induced cardiomyopathy, we injected 6 × 105 adult cardiomyocytes, 3 × 107 bone marrow cells, or both into damaged hearts, for myocardial repair. Coculture of the cardiomyocytes with the bone marrow cells enhanced the expression of integrin-β1D and focal adhesion kinase in cardiomyocytes, resulting in increased survival and decreased apoptosis of the cardiomyocytes after 7 days of culture. Compared with the baseline levels, cardiac function was preserved by the implantation of bone marrow cells alone and by the implantation of cardiomyocytes in combination with bone marrow cells, but it was decreased significantly 28 days after the implantation of cardiomyocytes alone. Furthermore, apoptosis of the host cardiomyocytes was decreased significantly after the implantation of bone marrow cells alone, or in combination with cardiomyocytes, compared with that after the implantation of cardiomyocytes alone (p < 0.01). Interestingly, the implantation of adult cardiomyocytes in combination with bone marrow cells resulted in a dramatic increase in the survival of donor cardiomyocytes, and induced the myogenic differentiation of donor bone marrow stem cells. Our findings indicate that cardiomyocytes and bone marrow cells can assist and compliment each other; thus, the implantation of adult cardiomyocytes in combination with bone marrow cells shows promise as a feasible new strategy for myocardial repair.
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spelling doaj.art-8b175ac44a8040be8e32193af6f8a4732022-12-21T19:00:04ZengSAGE PublishingCell Transplantation0963-68971555-38922008-06-011710.3727/096368908786092702Myocardial Repair Achieved by the Intramyocardial Implantation of Adult Cardiomyocytes in Combination with Bone Marrow CellsTao-Sheng Li M.D., Ph.D.0Masaya Takahashi1Mako Ohshima2Shu-Lan Qin3Masayuki Kubo4Keichi Muramatsu5Kimikazu Hamano6Department of Surgery and Clinical Science, Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, JapanDepartment of Surgery and Clinical Science, Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, JapanDepartment of Surgery and Clinical Science, Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, JapanDepartment of Surgery and Clinical Science, Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, JapanDepartment of Surgery and Clinical Science, Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, JapanDepartment of Surgery and Clinical Science, Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, JapanDepartment of Surgery and Clinical Science, Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, JapanVarious cytokines produced by bone marrow cells can protect adult cardiomyocytes against apoptosis. Thus, we investigated the feasibility of implanting adult cardiomyocytes in combination with bone marrow cells for myocardial repair. Ventricular cardiomyocytes were isolated from adult rats and cocultured with bone marrow cells. Using a rat model of doxorubicin-induced cardiomyopathy, we injected 6 × 105 adult cardiomyocytes, 3 × 107 bone marrow cells, or both into damaged hearts, for myocardial repair. Coculture of the cardiomyocytes with the bone marrow cells enhanced the expression of integrin-β1D and focal adhesion kinase in cardiomyocytes, resulting in increased survival and decreased apoptosis of the cardiomyocytes after 7 days of culture. Compared with the baseline levels, cardiac function was preserved by the implantation of bone marrow cells alone and by the implantation of cardiomyocytes in combination with bone marrow cells, but it was decreased significantly 28 days after the implantation of cardiomyocytes alone. Furthermore, apoptosis of the host cardiomyocytes was decreased significantly after the implantation of bone marrow cells alone, or in combination with cardiomyocytes, compared with that after the implantation of cardiomyocytes alone (p < 0.01). Interestingly, the implantation of adult cardiomyocytes in combination with bone marrow cells resulted in a dramatic increase in the survival of donor cardiomyocytes, and induced the myogenic differentiation of donor bone marrow stem cells. Our findings indicate that cardiomyocytes and bone marrow cells can assist and compliment each other; thus, the implantation of adult cardiomyocytes in combination with bone marrow cells shows promise as a feasible new strategy for myocardial repair.https://doi.org/10.3727/096368908786092702
spellingShingle Tao-Sheng Li M.D., Ph.D.
Masaya Takahashi
Mako Ohshima
Shu-Lan Qin
Masayuki Kubo
Keichi Muramatsu
Kimikazu Hamano
Myocardial Repair Achieved by the Intramyocardial Implantation of Adult Cardiomyocytes in Combination with Bone Marrow Cells
Cell Transplantation
title Myocardial Repair Achieved by the Intramyocardial Implantation of Adult Cardiomyocytes in Combination with Bone Marrow Cells
title_full Myocardial Repair Achieved by the Intramyocardial Implantation of Adult Cardiomyocytes in Combination with Bone Marrow Cells
title_fullStr Myocardial Repair Achieved by the Intramyocardial Implantation of Adult Cardiomyocytes in Combination with Bone Marrow Cells
title_full_unstemmed Myocardial Repair Achieved by the Intramyocardial Implantation of Adult Cardiomyocytes in Combination with Bone Marrow Cells
title_short Myocardial Repair Achieved by the Intramyocardial Implantation of Adult Cardiomyocytes in Combination with Bone Marrow Cells
title_sort myocardial repair achieved by the intramyocardial implantation of adult cardiomyocytes in combination with bone marrow cells
url https://doi.org/10.3727/096368908786092702
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