title: Myocardial repair achieved by the intramyocardial implantation of adult cardiomyocytes in combination with bone marrow cells.
abstract: 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 x 10(5) adult cardiomyocytes, 3 x 10(7) 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-beta1D 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.
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. litaoshe@yamaguchi-u.ac.jp
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.forename: Mako
authors.initials: M
authors.lastname: Ohshima
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Qin
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kubo
authors.forename: Keichi
authors.initials: K
authors.lastname: Muramatsu
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D009202:Cardiomyopathies / Q000139:chemically induced / Q000628:therapy; D002454:Cell Differentiation; D002470:Cell Survival; D018920:Coculture Techniques; D004317:Doxorubicin / Q000633:toxicity; D004452:Echocardiography; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000903:Antibiotics, Antineoplastic; D019012:Integrin beta1; D004317:Doxorubicin; D051416:Focal Adhesion Protein-Tyrosine Kinases